Role of Hepatic Deposited Immunoglobulin G in the Pathogenesis of Liver Damage in Systemic Lupus Erythematosus.

Abstract

The onset of hepatic disorders in patients with systemic lupus erythematosus (SLE) is frequent; however, the etiology and liver pathogenesis of SLE remain unknown. In the present study, the role of hepatic deposited immunoglobulin G (IgG) in SLE-derived liver damage was investigated. From a retrospective analysis of the medical records of 404 patients with lupus and from experimental studies on mice models, we found that liver dysfunction is common in SLE and liver damage with IgG deposition spontaneously develops in lupus-prone mice. Liver injury was recreated in mice by injecting IgG from lupus serum intrahepatically. The inflammation intensity in the liver decreased with IgG depletion and the lupus IgG-induced liver inflammation in FcγRIII-deficient mice was comparatively low; while, inflammation was increased in FcγRIIb-deficient mice. Macrophages, Kupffer cells, natural killer cells, and their products, but not lymphocytes, are required for the initiation of SLE-associated liver inflammation. Blocking IgG signaling using a spleen tyrosine kinase (Syk) inhibitor suppressed the liver damage. Our findings provided evidence of spontaneously established liver damage in SLE. They also suggested that hepatic-deposited lupus IgG is an important pathological factor in the development of liver injury and that hepatic inflammation is regulated by the Syk signaling pathway. Thus, Syk inhibition might promote the development of a therapeutic strategy to control liver damage in patients with SLE.

• Authors: Xiang Fang, Muhammad Haidar Zaman, Xuanxuan Guo, Huimin Ding, Changhao Xie, Xiaojun Zhang, Guo-Min Deng
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 1457 ( 2018) ISSN: 1664-3224 [Print] Switzerland
• PMID: 29988500 (Publication Type: Journal Article)