Anti-Human Serum Albumin Autoantibody May Be Involved in the Pathogenesis of Autoimmune Bullous Skin Diseases

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Background: A few previous studies suggested the presence of autoantibodies to unnatural human serum albumin (HSA), and our recent findings suggest that autoantibodies to natural HSA might also exist in vivo. Although effective immunological diagnostic systems for autoimmune bullous skin diseases (AIBD) have been established, there are still unidentified cutaneous autoantigens. Methods: In the present study, immunoprecipitation-immunoblotting, immunofluorescence assay and ELISAs were used to identify and quantify the anti-HSA autoantibodies in AIBD sera. Peptide ELISAs were used to confirm the epitopes recognized by anti-HSA autoantibodies in AIBD sera. In vitro cell and tissue culture models were employed to investigate the potential pathogenesis of anti-HSA autoantibody. Statistical analyses were used to study the correlation of anti-HSA autoantibody with the immunological and clinical features of AIBD patients. Findings: By immunoprecipitation-immunoblotting, immunofluorescence assay, anti-HSA autoantibodies could be detected in AIBD sera; by ELISAs, positive rates of AIBD sera for IgG and IgA anti-HSA autoantibodies were 29% and 34%, respectively. The IgG anti-HSA autoantibodies in ABID sera recognized a number of HSA antigen epitopes and therefore a polyclonal antibody against HSA were next employed to study its pathogenesis. With in vitro cell and tissue culture models, we proved that anti-HSA antibody was able to induce DNA damage, via activation of phospho-p38 signaling pathway. This is the first report that an autoantibody may induce DNA damage. Statistical analyses also proved that anti-HSA autoantibodies were positively correlated with various known autoantibodies and clinical features of ABID patients. Interpretation: IgG and IgA autoantibodies to HSA may have diagnosis values for AIBD, and may be also pathological autoantibodies. DNA damage might be involved in the pathogenic role of anti-HSA autoantibodies in AIBD. Phospho-p38 signaling pathway is a potential target for treatment of skin lesions of AIBD positive for serum anti-HSA autoantibodies. Funding Statement: This work was supported by National Science and Technology Major Project (2018ZX10101003), the Natural Science Foundation of Heilongjiang Province of China (QC2016129), the Scientific Research Foundation of First Affiliated Hospital of Harbin Medical University (2017B013), China; and the Research on Measures for Intractable Diseases' Project: matching fund subsidy of Ministry of Health Labour and Welfare, Japan (H24‐ 038). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: All studies were performed, following guidelines of Dermatology Hospital of Jiangxi Province, Harbin Medical University, Kurume University School of Medicine and Osaka City University Graduate School of Medicine. All participated patients or their legal guardians in this study provided informed consents, and these studies were conducted according to Declaration of Helsinki Principles. This study was reviewed and approved by the ethics committee of Harbin Medical University.