دورية أكاديمية
أعرض في EDS

Impaired proteolysis by SPPL2a causes CD74 fragment accumulation that can be recognized by anti-CD74 autoantibodies in human ankylosing spondylitis.

التفاصيل البيبلوغرافية
العنوان: Impaired proteolysis by SPPL2a causes CD74 fragment accumulation that can be recognized by anti-CD74 autoantibodies in human ankylosing spondylitis.
المؤلفون: van Kempen TS; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Leijten EFA; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Lindenbergh MFS; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Nordkamp MO; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Driessen C; Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Lebbink RJ; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands., Baerlecken N; Department of Clinical Immunology and Rheumatology, Medical University Hannover, Hannover, Germany., Witte T; Department of Clinical Immunology and Rheumatology, Medical University Hannover, Hannover, Germany., Radstake TRDJ; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Boes M; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Pediatrics, University Medical Center Utrecht, Utrecht, the Netherlands.
المصدر: European journal of immunology [Eur J Immunol] 2020 Aug; Vol. 50 (8), pp. 1209-1219. Date of Electronic Publication: 2020 Apr 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 1273201 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4141 (Electronic) Linking ISSN: 00142980 NLM ISO Abbreviation: Eur J Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: <2005->: Weinheim : Wiley-VCH
Original Publication: Weinheim, Verlag Chemie GmbH.
مواضيع طبية MeSH: Proteolysis*, Antigens, Differentiation, B-Lymphocyte/*immunology , Aspartic Acid Endopeptidases/*physiology , Autoantibodies/*immunology , Histocompatibility Antigens Class II/*immunology , Spondylitis, Ankylosing/*immunology, Adult ; Aged ; Antigens, Differentiation, B-Lymphocyte/metabolism ; Female ; HLA-DR Antigens/analysis ; Histocompatibility Antigens Class II/metabolism ; Humans ; Immunoglobulin G/immunology ; Interferon-gamma/pharmacology ; Male ; Middle Aged ; THP-1 Cells
مستخلص: Ankylosing spondylitis (AS) is associated with autoantibody production to class II MHC-associated invariant chain peptide, CD74/CLIP. In this study, we considered that anti-CD74/CLIP autoantibodies present in sera from AS might recognize CD74 degradation products that accumulate upon deficiency of the enzyme signal peptide peptidase-like 2A (SPPL2a). We analyzed monocytes from healthy controls (n = 42), psoriatic arthritis (n = 25), rheumatoid arthritis (n = 16), and AS patients (n = 15) for SPPL2a enzyme activity and complemented the experiments using SPPL2a-sufficient and -deficient THP-1 cells. We found defects in SPPL2a function and CD74 processing in a subset of AS patients, which culminated in CD74 and HLA class II display at the cell surface. These findings were verified in SPPL2a-deficient THP-1 cells, which showed expedited expression of MHC class II, total CD74 and CD74 N-terminal degradation products at the plasma membrane upon receipt of an inflammatory trigger. Furthermore, we observed that IgG anti-CD74/CLIP autoantibodies recognize CD74 N-terminal degradation products that accumulate upon SPPL2a defect. In conclusion, reduced activity of SPPL2a protease in monocytes from AS predisposes to endosomal accumulation of CD74 and CD74 N-terminal fragments, which, upon IFN-γ-exposure, is deposited at the plasma membrane and can be recognized by anti-CD74/CLIP autoantibodies.
(© 2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
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فهرسة مساهمة: Keywords: Ankylosing spondylitis; Autoimmunity; CD74; Monocytes; SPPL2a
المشرفين على المادة: 0 (Antigens, Differentiation, B-Lymphocyte)
0 (Autoantibodies)
0 (HLA-DR Antigens)
0 (Histocompatibility Antigens Class II)
0 (Immunoglobulin G)
0 (invariant chain)
82115-62-6 (Interferon-gamma)
EC 3.4.23.- (Aspartic Acid Endopeptidases)
EC 3.4.23.- (SPPL2a protein, human)
تواريخ الأحداث: Date Created: 20200322 Date Completed: 20201215 Latest Revision: 20210110
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7496470
DOI: 10.1002/eji.201948502
PMID: 32198923
قاعدة البيانات: MEDLINE
الوصف
تدمد:1521-4141
DOI:10.1002/eji.201948502