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. 2025 Jul 2;27(1):133.
doi: 10.1186/s13075-025-03600-0.

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

Chao Sun  1 , Hongxia Yang  1 , Yingfang Zhang  1 , Shiyu Wu  1 , Xinxin Zhang  1 , Wei Jiang  2 , Qinglin Peng  2 , Guochun Wang  1   2 , Xin Lu  3   4
Affiliations

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

Chao Sun et al. Arthritis Res Ther. .

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.

Keywords: Anti-interferon-α antibody; Dermatomyositis; Disease activity; MDA5; Prognosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the China-Japan Friendship Hospital (2019-SDZL-3). Consent for publication: All participants signed an informed consent agreement. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Detection of anti-IFN-α antibodies in anti-MDA5-DM patients. Serum anti-IFN-α antibodies were tested by an in-house ELISA. The dotted line represents the cut-off value calculated as the mean value of 55 HC samples plus a threefold standard deviation (A). Immunoblot results of four anti-MDA5-DM patients and two HCs. Lane 1–2, anti-IFN-α-positive sera of anti-MDA5-DM patients in ELISA tests, which immunoblotted bands at a molecular weight of approximately 19.2 kDa; Lane 3–4, anti-IFN-α-negative sera of anti-MDA5-DM patients in ELISA tests; Line 5–6, sera of healthy controls (B). Distribution of positivity rates of anti-IFN-α antibodies in different age groups (C). IFN: interferon; HC: healthy controls; MDA5: melanoma differentiation associated gene 5. *p < 0.05; ****p < 0.0001
Fig. 2
Fig. 2
Correlation analysis of anti-IFN-α antibody levels and disease activity of anti-MDA5-DM patients. Spearman’s correlation analyses were used to evaluate the association of anti-IFN-α antibody levels with the laboratory measures and disease activity. Fet: ferritin; PhGA: physician global disease activity; VAS: visual analogue scale
Fig. 3
Fig. 3
Longitudinal analysis of anti-IFN-α antibody levels with disease activities in anti-MDA5-DM patients. 13 patients with positive anti-IFN antibodies at the baseline were included. Generalized estimating equations (GEE) model was used for analysis
Fig. 4
Fig. 4
Changes of anti-IFN-α antibodies in different disease status compared to the baseline. Compared to baseline, changes of anti-IFN-α antibody levels in the disease aggravation or remission groups during follow-up (A-B); changes of anti-IFN-α antibody levels in the RP-ILD or non-RP-ILD groups during follow-up (C-D); changes of anti-IFN-α antibody levels in the infection or non-infection groups during follow-up (E-F)
Fig. 5
Fig. 5
Survival analysis of anti-MDA5-DM patients with anti-IFN-α antibodies. Cumulative survival rates were calculated using Kaplan-Meier test. IFN: interferon; po: positive; neg: negative; Ab: antibody. p < 0.05 as significance
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