Inflammatory myopathies

Myositis-specific autoantibodies recognising Mi2 also target the autoimmune regulator (AIRE) protein at a shared PHD zinc finger

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

Autoantibodies targeting Mi2 recognise AIRE at a shared PHD1 epitope - a conserved motif found in numerous transcriptional regulators.

Study context

Population
Patients with anti-Mi2 autoantibody-positive myositis; healthy controls, patients with myositis and those with other autoimmune diseases

Main finding

As reported in the abstract

  • Phage immunoprecipitation sequencing (PhIP-Seq) identified autoantibodies recognising AIRE in sera from anti-Mi2 autoantibody-positive patients
  • Both anti-AIRE and anti-Mi2 autoantibodies predominantly recognised a homologous region containing PHD1, critical for AIRE and Mi2/NuRD function
  • ELISA and luciferase immunoprecipitation system (LIPS): anti-Mi2-positive patients were positive for anti-AIRE autoantibodies; AIRE reactivity largely absent in healthy comparators, anti-Mi2-negative myositis and other autoimmune diseases
  • Affinity-purified anti-Mi2 autoantibodies recognised both Mi2 and AIRE by ELISA; anti-Mi2-depleted fractions recognised neither protein

Original publication

Myositis-specific autoantibodies recognising Mi2 also target the AIRE protein at a shared PHD zinc finger. Ann Rheum Dis. Published 15 September 2025. doi:10.1016/j.ard.2025.08.023

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