Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis

Abstract Background Interferons (IFN) are implicated in the pathogenesis of anti-MDA5 dermatomyositis (anti-MDA5-DM), but the presence of anti-IFN antibodies remains unclear. This study aims to assess serum levels of anti-IFN-α antibodies in anti-MDA5-DM patients and explore their clinical associati...

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Main Authors: Chao Sun, Hongxia Yang, Yingfang Zhang, Shiyu Wu, Xinxin Zhang, Wei Jiang, Qinglin Peng, Guochun Wang, Xin Lu
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Arthritis Research & Therapy
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Online Access:https://doi.org/10.1186/s13075-025-03600-0
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author Chao Sun
Hongxia Yang
Yingfang Zhang
Shiyu Wu
Xinxin Zhang
Wei Jiang
Qinglin Peng
Guochun Wang
Xin Lu
author_facet Chao Sun
Hongxia Yang
Yingfang Zhang
Shiyu Wu
Xinxin Zhang
Wei Jiang
Qinglin Peng
Guochun Wang
Xin Lu
author_sort Chao Sun
collection DOAJ
description Abstract Background Interferons (IFN) are implicated in the pathogenesis of anti-MDA5 dermatomyositis (anti-MDA5-DM), but the presence of anti-IFN antibodies remains unclear. This study aims to assess serum levels of anti-IFN-α antibodies in anti-MDA5-DM patients and explore their clinical associations. Methods Serum samples from 176 anti-MDA5-DM patients and 55 healthy controls were analyzed for anti-IFN-α antibody levels using an in-house ELISA assay, with immunoblot validation in a subset. Associations between anti-IFN-α antibodies and disease activity or prognosis were assessed. Results The prevalence of anti-IFN-α antibodies in anti-MDA5-DM patients was 17.6% (31/176), with higher rates in those aged over 60 years. Anti-IFN-α antibody-positive patients exhibited significantly higher incidences of RP-ILD (67.7% vs. 41.4%, p = 0.008) and pulmonary infections (74.2% vs. 46.2%, p = 0.005), with fungi, particularly Aspergillus, being the predominant pathogens. Serum anti-IFN-α antibody levels positively correlated with IgG (r = 0.48, p < 0.0001), ESR (r = 0.28, p = 0.003), ferritin (r = 0.16, p = 0.03), lung VAS (r = 0.24, p = 0.01), and PhGA VAS (r = 0.28, p = 0.002). Longitudinal analysis showed that changes in anti-IFN-α antibody levels paralleled changes in skin VAS, lung VAS, and PhGA VAS (p = 0.015, 0.005, and 0.004, respectively). Notably, treatment-aggravated cases had increased anti-IFN-α antibody levels from baseline (p = 0.017), while remission cases showed decreased levels (p = 0.004). Mortality was significantly higher in anti-IFN-α positive patients (Log-rank p = 0.006). Conclusion A subset of anti-MDA5-DM patients demonstrated positive serum anti-IFN-α antibodies. The significant association of these antibodies with disease activity and prognosis suggests their potential as a clinical biomarker. Monitoring anti-IFN-α antibody levels may provide an effective means to assess treatment response and predict outcomes in anti-MDA5-DM.
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spelling doaj-art-69d6fc2c7508416c99ec2d7a7e5f725d2025-08-20T03:03:38ZengBMCArthritis Research & Therapy1478-63622025-07-0127111010.1186/s13075-025-03600-0Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositisChao Sun0Hongxia Yang1Yingfang Zhang2Shiyu Wu3Xinxin Zhang4Wei Jiang5Qinglin Peng6Guochun Wang7Xin Lu8Peking University China-Japan Friendship School of Clinical MedicinePeking University China-Japan Friendship School of Clinical MedicinePeking University China-Japan Friendship School of Clinical MedicinePeking University China-Japan Friendship School of Clinical MedicinePeking University China-Japan Friendship School of Clinical MedicineDepartment of Rheumatology, China-Japan Friendship HospitalDepartment of Rheumatology, China-Japan Friendship HospitalPeking University China-Japan Friendship School of Clinical MedicinePeking University China-Japan Friendship School of Clinical MedicineAbstract Background Interferons (IFN) are implicated in the pathogenesis of anti-MDA5 dermatomyositis (anti-MDA5-DM), but the presence of anti-IFN antibodies remains unclear. This study aims to assess serum levels of anti-IFN-α antibodies in anti-MDA5-DM patients and explore their clinical associations. Methods Serum samples from 176 anti-MDA5-DM patients and 55 healthy controls were analyzed for anti-IFN-α antibody levels using an in-house ELISA assay, with immunoblot validation in a subset. Associations between anti-IFN-α antibodies and disease activity or prognosis were assessed. Results The prevalence of anti-IFN-α antibodies in anti-MDA5-DM patients was 17.6% (31/176), with higher rates in those aged over 60 years. Anti-IFN-α antibody-positive patients exhibited significantly higher incidences of RP-ILD (67.7% vs. 41.4%, p = 0.008) and pulmonary infections (74.2% vs. 46.2%, p = 0.005), with fungi, particularly Aspergillus, being the predominant pathogens. Serum anti-IFN-α antibody levels positively correlated with IgG (r = 0.48, p < 0.0001), ESR (r = 0.28, p = 0.003), ferritin (r = 0.16, p = 0.03), lung VAS (r = 0.24, p = 0.01), and PhGA VAS (r = 0.28, p = 0.002). Longitudinal analysis showed that changes in anti-IFN-α antibody levels paralleled changes in skin VAS, lung VAS, and PhGA VAS (p = 0.015, 0.005, and 0.004, respectively). Notably, treatment-aggravated cases had increased anti-IFN-α antibody levels from baseline (p = 0.017), while remission cases showed decreased levels (p = 0.004). Mortality was significantly higher in anti-IFN-α positive patients (Log-rank p = 0.006). Conclusion A subset of anti-MDA5-DM patients demonstrated positive serum anti-IFN-α antibodies. The significant association of these antibodies with disease activity and prognosis suggests their potential as a clinical biomarker. Monitoring anti-IFN-α antibody levels may provide an effective means to assess treatment response and predict outcomes in anti-MDA5-DM.https://doi.org/10.1186/s13075-025-03600-0Anti-interferon-α antibodyMDA5DermatomyositisDisease activityPrognosis
spellingShingle Chao Sun
Hongxia Yang
Yingfang Zhang
Shiyu Wu
Xinxin Zhang
Wei Jiang
Qinglin Peng
Guochun Wang
Xin Lu
Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis
Arthritis Research & Therapy
Anti-interferon-α antibody
MDA5
Dermatomyositis
Disease activity
Prognosis
title Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis
title_full Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis
title_fullStr Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis
title_full_unstemmed Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis
title_short Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis
title_sort anti interferon α antibodies associate with disease activity and prognosis in anti mda5 positive dermatomyositis
topic Anti-interferon-α antibody
MDA5
Dermatomyositis
Disease activity
Prognosis
url https://doi.org/10.1186/s13075-025-03600-0
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