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.
Highlights
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that possesses the feature of elevated autoantibodies and associated damage in the tissues of multiple organs [1,2,3]
The results showed that the severity of liver inflammation induced by lupus immunoglobulin G (IgG) was attenuated in mice treated with anti-asialo GM1 (ASGM1) Abs compared with that in mice not treated with anti-ASGM1 Abs (Figure 4D)
Our clinical study of patients with systemic lupus erythematosus (SLE) and practical experiments on animals demonstrated that liver injury is established in SLE and that hepatic deposition of lupus IgG is an important pathological factor in the development of SLEassociated liver injury
Summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that possesses the feature of elevated autoantibodies and associated damage in the tissues of multiple organs [1,2,3]. The relationship between SLE and variation in LFTs might be caused by three possibilities: [1] an overlap of SLE with another autoimmune liver disease; [2] comorbidity of SLE and a nonautoimmune hepatopathy; or [3] the existence of liver parenchymal injury that only relates to SLE (lupus hepatitis) [8, 9]. Intrahepatic Deposited IgG in Lupus-Hepatitis of liver injury ascribed by autoimmune mechanisms, such as autoimmune hepatitis (AIH) or primary biliary cirrhosis, with hepatopathies triggered by SLE [5, 10]. Patients with SLE have comorbidities with many non-autoimmune hepatic diseases, such as drug-derived hepatic injury, viral or infectious hepatitis, and thrombotic liver diseases [11,12,13,14]. It is important to understand the pathogenesis and features of lupus hepatitis
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.