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Identification of a novel autoantibody against heat shock factor 1 in idiopathic inflammatory myopathy
Ya-Mei Zhang1, Lin Liang2, Han-Bo Yang2
1Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, and Graduate School of Peking Union Medical College, Beijing, China.
Objectives:
Myositis autoantibodies show great utility in the diagnosis and clinico-serological phenotyping of idiopathic inflammatory myopathy (IIM). We identified a novel autoantibody against heat shock factor 1 (HSF1) and further evaluated its disease specificity and clinical significance in IIM patients.
Methods:
A human protein microarray was used to identify autoantibodies in myositis sera. ELISA, immunoblot and dot blot assays were applied to examine anti-HSF1 autoantibodies in IIM patients and controls. Immunofluorescence was used to detect HSF1 expression in muscle tissues.
Results:
Anti-HSF1 was identified as a novel autoantibody by protein microarray and the seroreactivity was confirmed by immunoprecipitation, ELISA, immunoblot and dot blot assays. Anti-HSF1 autoantibodies were present in 64/581 (11.0%) IIM, 4/37 (10.8%) rheumatoid arthritis, 5/40 (12.5%) primary Sjögren's syndrome, 2/40 (5%) systemic lupus erythematosus, while largely negative in healthy controls. Anti-HSF1 autoantibodies were significantly associated with pruritus, hypergammaglobulinaemia, and elevated erythrocyte sedimentation rate in IIM patients. Anti-HSF1 autoantibodies were more prevalent in cancer-associated myositis (CAM) compared to non-CAM patients (17.2% vs. 7.5%, p=0.009), nevertheless were undetectable in cancer controls. Meanwhile, cross-sectional and longitudinal analyses revealed positive correlations between anti-HSF1 levels and disease activity in IIM patients without cancer. Additionally, increased expression of HSF1 was found in regenerating muscle cells of myositis muscle tissues.
Conclusions:
These data reveal anti-HSF1 as a new autoantibody associated with CAM in IIM. The autoimmunity against HSF1 may be involved in the immunopathogenesis of myositis.
