دورية أكاديمية
Prediction of Erosive Disease Development by Antimitochondrial Antibodies in Rheumatoid Arthritis.
| العنوان: | Prediction of Erosive Disease Development by Antimitochondrial Antibodies in Rheumatoid Arthritis. |
|---|---|
| المؤلفون: | Moore RE; Division of Rheumatology, University of Washington, Seattle., Wang T; Division of Rheumatology, University of Washington, Seattle., Duvvuri B; Division of Rheumatology, University of Washington, Seattle., Feser ML; Division of Rheumatology, University of Colorado-Denver., Deane KD; Division of Rheumatology, University of Colorado-Denver., Solomon JJ; Center for Interstitial Lung Disease, National Jewish Health, Denver, Colorado., Nelson JL; Fred Hutchinson Cancer Research Center, Seattle, Washington., Demoruelle MK; Division of Rheumatology, University of Colorado-Denver., Lood C; Division of Rheumatology, University of Washington, Seattle. |
| المصدر: | Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2023 Jun; Vol. 75 (6), pp. 890-899. Date of Electronic Publication: 2023 Mar 29. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley Country of Publication: United States NLM ID: 101623795 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-5205 (Electronic) Linking ISSN: 23265191 NLM ISO Abbreviation: Arthritis Rheumatol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Malden, MA : Wiley, [2014]- |
| مواضيع طبية MeSH: | Arthritis, Rheumatoid*, Humans ; Cross-Sectional Studies ; Autoantibodies ; Anti-Citrullinated Protein Antibodies ; Enzyme-Linked Immunosorbent Assay ; Peptides, Cyclic |
| مستخلص: | Objective: Mitochondria are found in the extracellular space in rheumatoid arthritis (RA). However, whether mitochondria are a source of autoantigens in RA has not been carefully addressed. Thus, we undertook this study to investigate the presence and significance of antimitochondrial antibodies (AMAs) in patients with RA. Methods: AMAs were measured in serum samples from 3 cross-sectional cohorts of RA patients (n = 95, n = 192, and n = 117) and healthy individuals (n = 38, n = 72, and n = 50) using a flow cytometry-based assay. Further, AMAs were detected using an anti-mitofusin-1 (anti-MFN-1) IgG enzyme-linked immunosorbent assay and Western blot analysis. A longitudinal inception cohort, followed up for a median of 8 years, was used to study disease progression. Results: AMA levels were elevated in RA patients from all 3 cohorts as compared to healthy individuals (P < 0.001, P < 0.05, and P < 0.01), with a range of 14-26% positivity. Levels of anti-MFN-1 antibodies correlated with AMA levels (r = 0.31, P = 0.006) and were elevated in RA patients as compared to healthy individuals (P < 0.001). The presence of AMAs was associated with erosive disease (P < 0.05) and interstitial lung disease (P < 0.01). Further, AMA levels were found to predict erosive disease (odds ratio [OR] 4.59, P = 0.006) and joint space narrowing (OR 3.08, P = 0.02) independent of anti-citrullinated protein antibodies. Finally, anti-MFN-1 antibodies identified seronegative patients developing erosive disease (OR 9.33; P = 0.02). Conclusion: Our findings demonstrate the presence of novel autoantibodies targeting mitochondria in the setting of RA. AMAs were used to stratify patients based on disease phenotype and to predict development of erosive disease, including in patients with seronegative disease. Our results highlight the essential role of mitochondria in the pathogenesis of RA and suggest a possible benefit of therapies targeting mitochondrial-mediated inflammation and clearance in these patients. (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.) |
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| معلومات مُعتمدة: | K23 AR066712 United States AR NIAMS NIH HHS; P30 AR079369 United States AR NIAMS NIH HHS; R01 HL158606 United States HL NHLBI NIH HHS; UL1 TR002319 United States TR NCATS NIH HHS |
| المشرفين على المادة: | 0 (Autoantibodies) 0 (Anti-Citrullinated Protein Antibodies) 0 (Peptides, Cyclic) |
| تواريخ الأحداث: | Date Created: 20221229 Date Completed: 20230601 Latest Revision: 20240923 |
| رمز التحديث: | 20240923 |
| مُعرف محوري في PubMed: | PMC10238559 |
| DOI: | 10.1002/art.42428 |
| PMID: | 36580020 |
| قاعدة البيانات: | MEDLINE |
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