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<p>In this study, we present a comprehensive analysis of anti-cytokine autoantibodies (ACAAs)—autoimmune phenocopies that mimic genetic inborn errors of immunity (IEIs) and contribute to clinical variability during infections and autoimmune diseases. ACAAs were profiled in a multi-ethnic Asian cohort comprising healthy individuals and patients with diverse autoimmune and chronic health conditions. While ACAAs were infrequent in healthy individuals (&lt; 3%), their prevalence was significantly higher in patients with autoimmunity and multimorbidity, reaching up to 10% for certain interferon (IFN) subtypes. A functional assessment revealed that Type I anti-IFN autoantibodies elicited the strongest neutralising activities. This correlated with a reduction in pSTAT1 levels in cytokine-induced reporter cells. These findings suggest that type I anti-IFN antibodies can dampen/abrogate interferon signalling and may influence disease outcomes. Overall, these results map the landscape of ACAA frequency and specificity in an Asian population and underscore their context-dependent roles as modulators of cytokine networks, with potential implications for disease susceptibility and severity.</p>

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Profiling of immunomodulatory anti-cytokine autoantibodies associated with disease heterogeneity in a multiethnic Asian cohort

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月21日

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  • Bhuvaneshwari Shunmuganathan,
  • Rashi Gupta,
  • Ooiean Teng,
  • Isabelle Tan Siang Ling,
  • Bernadette Guek Cheng Er,
  • Nor Faizah Binte Mahmud,
  • Amy May Lin Quek,
  • Raymond Chee Seong Seet,
  • Paul A. MacAry

摘要

In this study, we present a comprehensive analysis of anti-cytokine autoantibodies (ACAAs)—autoimmune phenocopies that mimic genetic inborn errors of immunity (IEIs) and contribute to clinical variability during infections and autoimmune diseases. ACAAs were profiled in a multi-ethnic Asian cohort comprising healthy individuals and patients with diverse autoimmune and chronic health conditions. While ACAAs were infrequent in healthy individuals (< 3%), their prevalence was significantly higher in patients with autoimmunity and multimorbidity, reaching up to 10% for certain interferon (IFN) subtypes. A functional assessment revealed that Type I anti-IFN autoantibodies elicited the strongest neutralising activities. This correlated with a reduction in pSTAT1 levels in cytokine-induced reporter cells. These findings suggest that type I anti-IFN antibodies can dampen/abrogate interferon signalling and may influence disease outcomes. Overall, these results map the landscape of ACAA frequency and specificity in an Asian population and underscore their context-dependent roles as modulators of cytokine networks, with potential implications for disease susceptibility and severity.