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.

Systemic lupus erythematosus (SLE) is characterized by high levels of autoantibodies and multiorgan tissue damage. The pathogenesis of splenomegaly in SLE remains unknown. In this study, the role of immunoglobulin G (IgG) generation and deposition in the inflammation of the spleen and associated dysfunction in SLE was investigated. In the lupus mice, we observed the development of spontaneous splenomegaly, and we found that lupus serum IgG is an important pathological factor involved in the initiation of inflammation and further germinal center (GC) and plasma cell formation. We discovered that macrophages of the splenic marginal zone are dispensable for the GC response induced by lupus IgG, but red pulp macrophages are important for GC responses. Furthermore, we found that pathogenic lupus IgG promotes inflammation and GC formation through the macrophage-mediated secretion of TNF-α. Syk inhibitor treatment suppressed the changes in the histopathology of the spleen induced by lupus IgG. This study will contribute to the understanding of the pathogenesis of splenomegaly in lupus and promote the development of an effective therapeutic strategy for SLE.

Skin injury is the second most common clinical manifestation in patients with systemic lupus erythematosus (SLE). Neutrophils are crucial effector cells in the immune system but the significance of neutrophils in the pathogenesis of SLE is not clear. This study is to explore the role of neutrophils in the skin damage of SLE. We used lupus-prone mice and a C57BL/6 mouse model of lupus serum IgG-induced skin inflammation to investigate the role of neutrophils in skin damage of SLE. We found that a few neutrophils infiltrated the inflammatory sites of skin in lupus-prone mice and the lupus-IgG-induced skin damage mouse model. Depletion of neutrophils did not affect the development of skin inflammation caused by lupus IgG, and lupus IgG can induce apoptosis of neutrophils. The apoptosis of neutrophils induced by lupus IgG is related to FcγRIII and Fas/Fas ligand pathways. Our study indicates that neutrophils are not major contributors in the skin damage caused by tissue-deposited lupus IgG but death of neutrophils caused by lupus IgG may provide a resource of a large amount of autoantigens in SLE.