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

Fang, Xiang; Zaman, Muhammad Haidar; Guo, Xiamei; Ding, Huimin; Xie, Changhao; Zhang, Xiaojun; Deng, Guo-Min

doi:10.3389/fimmu.2018.01457

Cited by 27 publications

(41 citation statements)

References 51 publications

(56 reference statements)

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“…Autoantibodies are involved in the pathogenesis of autoimmune diseases (17). Previous studies showed that lupus patient serum induces tissue damage (18)(19)(20). Serum IgG from lupus patients activates inflammatory cells, such as monocytes/macrophages, dendritic cells and neutrophils, which produce cytokines and subsequently induce tissue damage (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 99%

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

et al. 2020

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“…Elevated level of serum IgG is a poor prognostic factor for autoimmune hepatitis associated with SLE. Additionally, the deposition of IgG is reported to cause tissue damage [24,25]. The serum IgG levels correlated with the serologic activity and can predict disease ares in patients with LN.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis identified salivary immunoglobulin gamma-3 chain C as a potential biomarker for systemic lupus erythematosus

Jung¹,

Nam²,

Ryu³

et al. 2020

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Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies and systemic inflammatory response. We aimed to characterize the salivary protein components and find biomarkers in patients with SLE. Methods The pooled salivary proteins of patients with SLE and healthy controls were subjected to 2-dimensional gel electrophoresis. The spots exhibiting > 2-fold intensity change between SLE and healthy controls were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Results The proteomic analysis using 2-dimensional gel electrophoresis and mass spectrometry revealed 10 differentially expressed protein spots, which included immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region (IGHA1), protein S100, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine deoxyribonucleic acid glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels than patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively, p < 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively, p < 0.001 for both). The salivary IGHG3 levels correlated with erythrocyte sedimentation rate (r = 0.26, p = 0.01), anti-double-strand deoxyribonucleic acid antibody levels (r = 0.25, p = 0.01), and nephritis (r = 0.28, p = 0.01). Conclusions Patients with SLE exhibited elevated salivary IGHG3 and lactoferrin levels, and the salivary IGHG3 levels correlated with disease activity markers of SLE. Salivary IGHG3 may be a promising non-invasive biomarker in SLE.

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“…15 We previously reported that monocytes/macrophages play an important role in the development of skin and liver inflammation that is induced by IgG deposition. 16,17 Furthermore, we demonstrated that monocytes/macrophage are required for inflammatory arthritis induced by bacterial DNA. 18 However, it remains currently unknown whether and how autoantibody IgG and inflammatory cells contribute to the development of arthritis in SLE, and why bone erosions fail to develop in SLEassociated arthritis.…”

Section: Introductionmentioning

confidence: 87%

“…Monocytes/macrophages are required for the development of skin and liver inflammation induced by lupus IgG. 16,17 Thus, we aimed to determine the role of monocytes/macrophages in the development of arthritis induced by lupus IgG using etoposides which selectively deplete monocytes/macrophages. Monocyte depletion resulted in significantly reduced arthritis in mice ( Figure 3a).…”

Section: Lupus Igg Depositions Cause Arthritis Through Monocytes/macrmentioning

confidence: 99%

Lupus IgG deposition causes arthritis but inhibits bone destruction through competitive occupation of FcγRI and reduced RANKL signalling

et al. 2020

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Objectives. Bone destruction is a remarkable feature of inflammatory arthritis. It remains unknown why arthritis associated with the systemic autoimmune/inflammatory condition systemic lupus erythematosus (SLE) does not result in erosion and destruction. We aimed to determine the role of autoantibody in the pathogenesis of non-erosive arthritis in SLE. Methods. We analysed medical record of SLE patients, investigated whether autoantibody induces arthritis lacking bone destruction in animal models and determined whether SLE autoantibody inhibits osteoclastogenesis induced by RANKL in vitro experiments. Results. We found that arthritis lacking bone erosions is common in SLE patients and lupus-prone mice. Intraarticular injection of lupus serum or IgG induces immune complex deposition and arthritis, but does not result in bone destruction. Deposition of IgG, monocytes/macrophages and TNF-a is all required for the development of arthritis. Lupus serum or IgG inhibits RANKLinduced differentiation of monocytes into osteoclast in a dosedependent manner. FccR acts as co-receptors for RANKL and is involved in osteoclastogenesis. Deficiency of FccRII or FccRIII does not affect osteoclastogenesis in the presence of SLE IgG. However, lupus IgG competes for FccRI binding with RANKL, thereby reducing osteoclastogenesis. Conclusion. Observations from this study demonstrate that IgG from SLE patients can induce arthritis and inhibits RANKL-induced osteoclastogenesis through competitive occupation of FccRI on monocytes/macrophages. This study improves the understanding of the pathophysiology of SLEassociated arthritis and offers a protective mechanism (FccRI inhibition) that may be targeted in other forms of autoimmune/ inflammatory arthritis, such as RA, to prevent or limit bone erosion and inflammatory bone loss.

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

Cited by 27 publications

References 51 publications

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

Proteomic analysis identified salivary immunoglobulin gamma-3 chain C as a potential biomarker for systemic lupus erythematosus

Lupus IgG deposition causes arthritis but inhibits bone destruction through competitive occupation of FcγRI and reduced RANKL signalling

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