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Background <p>The objective of this study was to characterise interleukin-6 (IL-6) pathway activity in idiopathic inflammatory myopathies (IIM) and investigate the contribution of circulating IL-6, soluble IL-6 receptor (sIL-6R) and anti-IL-6 autoantibodies to systemic IL-6 signalling.</p> Methods <p>IL-6 pathway activity was assessed in skeletal muscle transcriptomic data from patients with IIM and healthy controls. Serum samples from 51 patients with IIM and 32 controls were analysed for IL-6, sIL-6R and anti-IL-6 autoantibodies by ELISA. The capacity of serum to modulate IL-6 signalling in serum was quantified using a reporter gene assay (RGA).</p> Results <p>Transcriptomic analysis revealed enrichment of IL-6/JAK/STAT3 signalling in IIM muscle tissue across disease subtypes. Serum IL-6 levels were increased in IIM, while sIL-6R concentrations were comparable to those in controls. In contrast, anti-IL-6 autoantibody levels were reduced, particularly in dermatomyositis. Despite variability in individual components, serum from patients with IIM induced markedly increased IL-6 signalling activity in the RGA compared with controls. This enhanced signalling was independent of endogenous IL-6 concentrations and persisted in treated patients. Anti-IL-6 autoantibodies displayed moderate-to-high avidity and demonstrated neutralising capacity in vitro. Increased IL-6 signalling activity showed a negative association trend with muscle strength in newly diagnosed patients.</p> Conclusions <p>IIM is characterised by enhanced systemic IL-6 pathway activity that is not explained by circulating IL-6 levels alone but rather reflects a dysregulated cytokine milieu. Reduced levels of endogenous anti-IL-6 autoantibodies, together with their neutralising capacity, suggest a potential role in modulating IL-6 bioactivity.</p>

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Dysregulated IL-6 pathway activity in idiopathic inflammatory myopathies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月21日

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  • Anja Srpčič,
  • Felicita Urzi,
  • Manca Ogrič,
  • Mojca Frank Bertoncelj,
  • Saša Čučnik,
  • Polonca Mali,
  • Sergej Pirkmajer,
  • Katja Lakota,
  • Katja Perdan Pirkmajer

摘要

Background

The objective of this study was to characterise interleukin-6 (IL-6) pathway activity in idiopathic inflammatory myopathies (IIM) and investigate the contribution of circulating IL-6, soluble IL-6 receptor (sIL-6R) and anti-IL-6 autoantibodies to systemic IL-6 signalling.

Methods

IL-6 pathway activity was assessed in skeletal muscle transcriptomic data from patients with IIM and healthy controls. Serum samples from 51 patients with IIM and 32 controls were analysed for IL-6, sIL-6R and anti-IL-6 autoantibodies by ELISA. The capacity of serum to modulate IL-6 signalling in serum was quantified using a reporter gene assay (RGA).

Results

Transcriptomic analysis revealed enrichment of IL-6/JAK/STAT3 signalling in IIM muscle tissue across disease subtypes. Serum IL-6 levels were increased in IIM, while sIL-6R concentrations were comparable to those in controls. In contrast, anti-IL-6 autoantibody levels were reduced, particularly in dermatomyositis. Despite variability in individual components, serum from patients with IIM induced markedly increased IL-6 signalling activity in the RGA compared with controls. This enhanced signalling was independent of endogenous IL-6 concentrations and persisted in treated patients. Anti-IL-6 autoantibodies displayed moderate-to-high avidity and demonstrated neutralising capacity in vitro. Increased IL-6 signalling activity showed a negative association trend with muscle strength in newly diagnosed patients.

Conclusions

IIM is characterised by enhanced systemic IL-6 pathway activity that is not explained by circulating IL-6 levels alone but rather reflects a dysregulated cytokine milieu. Reduced levels of endogenous anti-IL-6 autoantibodies, together with their neutralising capacity, suggest a potential role in modulating IL-6 bioactivity.