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Background <p>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.</p> Methods <p>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.</p> Results <p>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%, <i>p</i> = 0.008) and pulmonary infections (74.2% vs. 46.2%, <i>p</i> = 0.005), with fungi, particularly Aspergillus, being the predominant pathogens. Serum anti-IFN-α antibody levels positively correlated with IgG (<i>r</i> = 0.48, <i>p</i> &lt; 0.0001), ESR (<i>r</i> = 0.28, <i>p</i> = 0.003), ferritin (<i>r</i> = 0.16, <i>p</i> = 0.03), lung VAS (<i>r</i> = 0.24, <i>p</i> = 0.01), and PhGA VAS (<i>r</i> = 0.28, <i>p</i> = 0.002). Longitudinal analysis showed that changes in anti-IFN-α antibody levels paralleled changes in skin VAS, lung VAS, and PhGA VAS (<i>p</i> = 0.015, 0.005, and 0.004, respectively). Notably, treatment-aggravated cases had increased anti-IFN-α antibody levels from baseline (<i>p</i> = 0.017), while remission cases showed decreased levels (<i>p</i> = 0.004). Mortality was significantly higher in anti-IFN-α positive patients (Log-rank <i>p</i> = 0.006).</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月2日

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  • Chao Sun,
  • Hongxia Yang,
  • Yingfang Zhang,
  • Shiyu Wu,
  • Xinxin Zhang,
  • Wei Jiang,
  • Qinglin Peng,
  • Guochun Wang,
  • Xin Lu

摘要

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.