دورية أكاديمية
The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort.
| العنوان: | The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort. |
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| المؤلفون: | Barron KS; National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Aksentijevich I; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Deuitch NT; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Stone DL; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Hoffmann P; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Videgar-Laird R; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Soldatos A; National Institute of Neurological Diseases and Strokes, National Institutes of Health (NIH), Bethesda, MD, United States., Bergerson J; National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Toro C; Undiagnosed Disease Program, National Institutes of Health (NIH), Bethesda, MD, United States., Cudrici C; National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Nehrebecky M; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Romeo T; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Jones A; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Boehm M; National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Kanakry JA; National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Dimitrova D; National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Calvo KR; Department of Laboratory Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States., Alao H; National Institute of Digestive Diseases and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Kapuria D; National Institute of Digestive Diseases and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Ben-Yakov G; National Institute of Digestive Diseases and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Pichard DC; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Hathaway L; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Brofferio A; National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD, United States., McRae E; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Moura NS; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Schnappauf O; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Rosenzweig S; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Heller T; National Institute of Digestive Diseases and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Cowen EW; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Kastner DL; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Ombrello AK; National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, United States. |
| المصدر: | Frontiers in immunology [Front Immunol] 2022 Jan 10; Vol. 12, pp. 811473. Date of Electronic Publication: 2022 Jan 10 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Observational Study; Research Support, N.I.H., Intramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Adenosine Deaminase/*deficiency , Intercellular Signaling Peptides and Proteins/*deficiency, Adolescent ; Adult ; Aged ; COVID-19/metabolism ; Child ; Child, Preschool ; Cohort Studies ; Female ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Infant ; Longitudinal Studies ; Male ; Middle Aged ; Tumor Necrosis Factor Inhibitors/metabolism ; Young Adult |
| مستخلص: | The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease that has undergone extensive phenotypic expansion since being first described in patients with fevers, recurrent strokes, livedo racemosa, and polyarteritis nodosa in 2014. It is now recognized that patients may develop multisystem disease that spans multiple medical subspecialties. Here, we describe the findings from a large single center longitudinal cohort of 60 patients, the broad phenotypic presentation, as well as highlight the cohort's experience with hematopoietic cell transplantation and COVID-19. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic, however, most patients presented with significant overlap between these three phenotype groups. The cardinal features of the inflammatory/vascular group included cutaneous manifestations and stroke. Evidence of immune dysregulation was commonly observed, including hypogammaglobulinemia, absent to low class-switched memory B cells, and inadequate response to vaccination. Despite these findings, infectious complications were exceedingly rare in this cohort. Hematologic findings including pure red cell aplasia (PRCA), immune-mediated neutropenia, and pancytopenia were observed in half of patients. We significantly extended our experience using anti-TNF agents, with no strokes observed in 2026 patient months on TNF inhibitors. Meanwhile, hematologic and immune features had a more varied response to anti-TNF therapy. Six patients received a total of 10 allogeneic hematopoietic cell transplant (HCT) procedures, with secondary graft failure necessitating repeat HCTs in three patients, as well as unplanned donor cell infusions to avoid graft rejection. All transplanted patients had been on anti-TNF agents prior to HCT and received varying degrees of reduced-intensity or non-myeloablative conditioning. All transplanted patients are still alive and have discontinued anti-TNF therapy. The long-term follow up afforded by this large single-center study underscores the clinical heterogeneity of DADA2 and the potential for phenotypes to evolve in any individual patient. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors IA, DLK, and AO. (Copyright © 2022 Barron, Aksentijevich, Deuitch, Stone, Hoffmann, Videgar-Laird, Soldatos, Bergerson, Toro, Cudrici, Nehrebecky, Romeo, Jones, Boehm, Kanakry, Dimitrova, Calvo, Alao, Kapuria, Ben-Yakov, Pichard, Hathaway, Brofferio, McRae, Moura, Schnappauf, Rosenzweig, Heller, Cowen, Kastner and Ombrello.) |
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| فهرسة مساهمة: | Keywords: ADA2; anti-TNF therapy; bone marrow failure; deficiency of adenosine deaminase 2 (DADA2); hematopoietic cell transplantation (HCT); immune dysregulation; lacunar strokes; vasculopathy |
| المشرفين على المادة: | 0 (Intercellular Signaling Peptides and Proteins) 0 (Tumor Necrosis Factor Inhibitors) EC 3.5.4.4 (ADA2 protein, human) EC 3.5.4.4 (Adenosine Deaminase) |
| تواريخ الأحداث: | Date Created: 20220131 Date Completed: 20220209 Latest Revision: 20220209 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8790931 |
| DOI: | 10.3389/fimmu.2021.811473 |
| PMID: | 35095905 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.811473 |