Background and aims Although arthritis is frequent in patients with systemic lupus erythematosus (SLE), its pathogenesis remains unclear. The aim in our study is to investigate the pathognesis of arthritis in SLE.
Methods We analysed the feature of SLE patients with arthritis and lupus-prone mice with arthritis, investigated the role of joint deposited IgG in the development of lupus arthritis.
Results Arthritis lacking bone erosion is common symptom in most of SLE patients and spontaneously develops in lupus prone mice. Large amount of IgG deposited in joint of lupus prone mice. Similar arthritis to lupus prone mice was induced by intraarticular injection of lupus IgG and was dependent on the dose of lupus IgG. Joint deposited IgG, monocytes/macrophages and TNFa were required in the development of lupus arthritis. Joint deposited lupus IgG inhibited RANKL-induced osteoclastogenesis in dose and time dependent manner. Lacking ITAM containing FcγRIII reduced inhibitory effect of lupus IgG on osteoclastogenesis. Lupus IgG quickly stimulated Syk activation than RANKL through lipid rafts. Lupus IgG-induced Syk activation is related to dsDNA Ab. Blocking of Syk significantly inhibited arthritis induced by lupus IgG and arthritis in lupus prone mice, suppressed Syk activation induced by lupus IgG and osteoclastogenesis induced by RANKL.
Conclusions The joint deposited IgG exerts an important role in the development of lupus arthritis lacking of bone destruction, Syk plays a crucial role in lupus IgG-induced arthritis and inhibited osteoclastogenesis. This finding will promote development of effective therapeutic strategy to arthritis in SLE patients.
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