Anti‐heat shock protein 10 IgG in chronic spontaneous urticaria: Relation with miRNA‐101‐5p and platelet‐activating factor.

Background: Anti‐heat shock protein (HSP) autoantibodies are detected in autoimmune diseases. We sought to ascertain whether anti‐HSP10 IgG is present in patients with CSU and to elucidate the role of HSP10 in CSU pathogenesis. Method: Using a human proteome microarray, six potential autoantibodies had higher expression in 10 CSU samples compared with 10 normal controls (NCs). Among them, HSP10 IgG autoantibody was quantified by immune dot‐blot assay in sera from 86 CSU patients and 44 NCs. The serum levels of HSP10 and microRNA‐101‐5p were measured in CSU patients and NCs. The effects of HSP10 and miR‐101‐5p on mast cell degranulation in response to IgE, compound 48/80, and platelet‐activating factor (PAF) were investigated. Results: CSU patients had higher IgG positivity to HSP10 (40.7% vs. 11.4%, p =.001), lower serum HSP10 levels (5.8 ± 3.6 vs. 12.2 ± 6.6 pg/mL, p <.001) than in NCs, and their urticaria severity was associated with anti‐HSP10 IgG positivity, while HSP10 levels were related to urticaria control status. MiR‐101‐5p was increased in CSU patients. PAF enhanced IL4 production in PBMCs from CSU patients. IL‐4 upregulated miR‐101‐5p and reduced HSP10 expression in keratinocytes. Transfection of miR‐101‐5p reduced HSP10 expression in keratinocytes. MiR‐101‐5p promoted PAF‐induced mast cell degranulation, while HSP10 specifically prevented it. Conclusion: A new autoantibody, anti‐HSP10 IgG was detected in CSU patients, which showed a significant correlation with UAS7 scores. A decreased serum HSP10 level was associated with upregulation of miR‐101‐5p due to increased IL‐4 and PAF in CSU patients. Modulation of miR‐101‐5p and HSP10 may be a novel therapeutic approach for CSU. [ABSTRACT FROM AUTHOR]