Iguratimod, A Novel Immunomodulator, Ameliorated Lupus‐like Disease In MRL/lpr Mice With Redressed B Cell Differentiation

Objective Iguratimod is a small molecular immunomodulatory drug and has been approved for treating rheumatoid arthritis. Previous work revealed its inhibitory effects on humoral immunity. This study is performed to investigate effects of iguratimod on an antibody‐mediated disease and its possible mechanism.Methods Female MRL/lpr mice were treated with iguratimod, vehicle solution or cyclophosphamide. Their serum anti‐double strand DNA antibody was measured with radioimmunoassay. Kidney Ig G and CD20 were stained with immunohistochemistry and kidney injury was blindly scored by a renal pathologist. Splenic lymphocyte and B cell subset phenotype was analyzed with flowcytometry. Lymphocyte apoptosis were analyzed with annexin V/PI staining in vivo and with Brd U staining in vitro through flowcytometry.Results MRL/lpr mice treated with iguratimod showed milder signs of nephritis and arthritis, as well as disease activity markers in sera, compared to vehicle solution control group. Their abnormal B220+ T cell and plasma cell in spleen dropped down after iguratimod treatment yet their total B cell populations were recovered. Their skewed ratios of germinal center, marginal zone, follicular and transitional B cells partially rebalanced upon iguratimod other thancyclophosphamide treatment. Levels of cytokines that promote B cell activation and plasma cell maintaining were decreased by iguratimod. Iguratimod had no significant effects on cell proliferation or apoptosis. No overt side effects were observed.Conclusion Iguratimod could ameliorate lupus‐like disease in MRL/lpr mice probably through redressing abnormal B cell differentiation in a non‐antiproliferative manner. Our data suggest a potential therapeutic role of iguratimod in lupus.