Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory Syndrome.

التفاصيل البيبلوغرافية
العنوان:	Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory Syndrome.
المؤلفون:	Baghdassarian H; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Blackstone SA; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Clay OS; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Philips R; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Matthiasardottir B; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Nehrebecky M; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Hua VK; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., McVicar R; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Liu Y; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Tucker SM; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Randazzo D; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Deuitch N; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Rosenzweig S; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Mark A; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Sasik R; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Fisch KM; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Pimpale Chavan P; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Eren E; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Watts NR; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Ma CA; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Gadina M; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Schwartz DM; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Sanyal A; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Werner G; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Murdock DR; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Horita N; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Chowdhury S; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Dimmock D; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Jepsen K; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Remmers EF; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Goldbach-Mansky R; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Gahl WA; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., O'Shea JJ; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Milner JD; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Lewis NE; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Chang J; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Kastner DL; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Torok K; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Oda H; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Putnam CD; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.)., Broderick L; From the Bioinformatics and Systems Biology Program (H.B.), the Department of Pediatrics (H.B., O.S.C., V.K.H., N.E.L.), the Center for Computational Biology and Bioinformatics, Department of Medicine (A.M., R.S., K.M.F.), the Institute for Genomic Medicine (K.J.), the Department of Bioengineering (N.E.L.), the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics (J.C., L.B.), and the Department of Medicine (C.D.P.), University of California, San Diego, Sanford Burnham Prebys Medical Discovery Institute (R.M., Y.L.), and the San Diego Branch, Ludwig Institute for Cancer Research (C.D.P.), La Jolla, and the Department of Pathology (S.M.T.), Rady Children's Institute for Genomic Medicine (S.C., D.D.), and Rady Children's Hospital Foundation (J.C., L.B.), Rady Children's Hospital, San Diego - all in California; the Inflammatory Disease Section (S.A.B., B.M., M.N., S.R., P.P.C., N.H., E.F.R., D.L.K., H.O.), the Oncogenesis and Development Section (N.D.), and the Undiagnosed Diseases Program, Medical Genetics Branch (D.R.M., W.A.G.), National Human Genome Research Institute, the Molecular Immunology and Inflammation Branch (R.P., J.J.O.), the Light Imaging Section (D.R.) and the Translational Immunology Section (M.G.), Office of Science and Technology, and the Protein Expression Laboratory (E.E., N.R.W.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases (C.A.M.), and the Translational Autoinflammatory Disease Section (R.G.-M.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park (B.M.) - all in Maryland; Sanford School of Medicine, University of South Dakota, Sioux Falls (S.A.B.); the Division of Rheumatology and Clinical Immunology, University of Pittsburgh (D.M.S.), University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh (A.S., G.W., K.T.), and the University of Pittsburgh Scleroderma Center (A.S., G.W., K.T.) - all in Pittsburgh; the Division of Pediatric Allergy, Immunology, and Rheumatology, Columbia University, New York (J.D.M.); and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and the Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (H.O.).
المصدر:	The New England journal of medicine [N Engl J Med] 2023 Jun 15; Vol. 388 (24), pp. 2241-2252. Date of Electronic Publication: 2023 May 31.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1533-4406 (Electronic) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Boston, Massachusetts Medical Society.
مواضيع طبية MeSH:	Janus Kinases/antagonists & inhibitors , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/genetics , Autoimmune Diseases/drug therapy , Autoimmune Diseases/genetics , Dermatologic Agents/therapeutic use, Nitriles ; Pyrazoles/therapeutic use ; Pyrazoles/pharmacology ; Pyrimidines ; Mutation, Missense ; Gain of Function Mutation ; Anti-Inflammatory Agents/therapeutic use
مستخلص:	Background: Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high. Methods: We evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM. Genomic sequencing independently identified three heterozygous variants in a specific region of the gene that encodes signal transducer and activator of transcription 4 ( STAT4 ). Primary skin fibroblast and cell-line assays were used to define the functional nature of the genetic defect. We also assayed gene expression using single-cell RNA sequencing of peripheral-blood mononuclear cells to identify inflammatory pathways that may be affected in DPM and that may respond to therapy. Results: Genome sequencing revealed three novel heterozygous missense gain-of-function variants in STAT4 . In vitro, primary skin fibroblasts showed enhanced interleukin-6 secretion, with impaired wound healing, contraction of the collagen matrix, and matrix secretion. Inhibition of Janus kinase (JAK)-STAT signaling with ruxolitinib led to improvement in the hyperinflammatory fibroblast phenotype in vitro and resolution of inflammatory markers and clinical symptoms in treated patients, without adverse effects. Single-cell RNA sequencing revealed expression patterns consistent with an immunodysregulatory phenotype that were appropriately modified through JAK inhibition. Conclusions: Gain-of-function variants in STAT4 caused DPM in the families that we studied. The JAK inhibitor ruxolitinib attenuated the dermatologic and inflammatory phenotype in vitro and in the affected family members. (Funded by the American Academy of Allergy, Asthma, and Immunology Foundation and others.). (Copyright © 2023 Massachusetts Medical Society.)
التعليقات:	Comment in: N Engl J Med. 2023 Sep 21;389(12):1151. (PMID: 37733320) Comment in: N Engl J Med. 2023 Sep 21;389(12):1151-1152. (PMID: 37733321)
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معلومات مُعتمدة:	National Human Genome Research Institute, Intramur United States NH NIH HHS; T32 GM008806 United States GM NIGMS NIH HHS; ZID AR041180 United States ImNIH Intramural NIH HHS; UL1TR001442 United States NH NIH HHS; UL1 TR001442 United States TR NCATS NIH HHS; National Institute of Arthritis and Musculoskeleta United States NH NIH HHS; UH2 AI153029 United States AI NIAID NIH HHS; S10 OD026929 United States OD NIH HHS; UH2 AI153029 United States NH NIH HHS; R35 GM119850 United States GM NIGMS NIH HHS; FI2 GM137942 United States GM NIGMS NIH HHS; Undiagnosed Diseases Network United States NH NIH HHS; R35 GM119850 United States NH NIH HHS; T32GM8806 United States NH NIH HHS; 1Fi2GM137942-01 United States NH NIH HHS
المشرفين على المادة:	EC 2.7.10.2 (Janus Kinases) 0 (Nitriles) 0 (Pyrazoles) 0 (Pyrimidines) 82S8X8XX8H (ruxolitinib) 0 (STAT4 protein, human) 0 (Dermatologic Agents) 0 (Anti-Inflammatory Agents)
تواريخ الأحداث:	Date Created: 20230531 Date Completed: 20230617 Latest Revision: 20231216
رمز التحديث:	20231216
مُعرف محوري في PubMed:	PMC10392571
DOI:	10.1056/NEJMoa2202318
PMID:	37256972
قاعدة البيانات:	MEDLINE

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تدمد:	1533-4406
DOI:	10.1056/NEJMoa2202318