系统性红斑狼疮
免疫学
自身免疫
人性化鼠标
自身抗体
抗体
狼疮性肾炎
外周血单个核细胞
自身免疫性疾病
免疫系统
医学
点头老鼠
红斑狼疮
B细胞
生物
疾病
内科学
体外
生物化学
作者
Nikolina Mihaylova,Petroslav Chipinski,Silvya Bradyanova,Tsvetelina Velikova,Ekaterina Ivanova‐Todorova,Stela Chausheva,Melinda Herbáth,Desislava Kalinova,József Prechl,Dobroslav Kyurkchiev,Andrey Tchorbanov
摘要
Summary Systemic lupus erythematosus is a chronic inflammatory disease which involves multiple organs. Self-specific B and T cells play a main role in the pathogenesis of lupus and have been defined as a logical target for selective therapy. The protein annexin A1 (ANX A1) is a modulator of the immune system involving many cell types. An abnormal expression of ANX A1 was found on activated B and T cells during autoimmunity, suggesting its importance as a potential therapeutic target. We hypothesize that it may be possible to down-regulate the activity of autoreactive T and B cells from lupus patients in a humanized immunodeficient mouse model by treating them with an antibody against ANX A1. When cultured in the presence of anti-ANX A1, peripheral blood mononuclear cells (PBMC) from lupus patients showed a decreased number of immunoglobulin (Ig)G anti-dsDNA antibody-secreting plasma cells, decreased T cell proliferation and expression of activation markers and increased B and T cell apoptosis. We employed a humanized model of SLE by transferring PBMCs from lupus patients to immunodeficient non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. The humanized animals presented autoantibodies, proteinuria and immunoglobulin deposition in the renal glomeruli. Treatment of these NOD-SCID mice with an anti-ANX A1 antibody prevented appearance of anti-DNA antibodies and proteinuria, while the phosphate-buffered saline (PBS)-injected animals had high levels after the transfer. The treatment reduced the levels of autoantibodies to several autoantigens, lupus-associated cytokines and disease symptoms.
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