Discovery and characterization of cross-reactive intrahepatic antibodies in severe alcoholic hepatitis

Ali Reza Ahmadi, Guang Song, Tianshun Gao, Jing Ma, Xiaomei Han, Ming Wen Hu, Andrew M. Cameron, Russell N. Wesson, Benjamin Philosophe, Shane Ottmann, Elizabeth King, Ahmet Gurakar, Le Qi, Brandon Peiffer, James Burdick, Robert Anders, Zhanxiang Zhou, Hongkun Lu, Dechun Feng, Chien Sheng ChenJiang Qian, Bin Gao, Heng Zhu, Zhaoli Sun

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig-and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig-and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.

原文English
文章編號RP86678
期刊eLife
12
DOIs
出版狀態Published - 2023

All Science Journal Classification (ASJC) codes

  • 一般神經科學
  • 一般生物化學,遺傳學和分子生物學
  • 一般免疫學和微生物學

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