Abstract
Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lupus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0.5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent antibody intervention group (injected with 200 μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, followed by three times of injection with an interval of one month) and model group (injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the activation of immune-related cells in spleen. Levels of autoantibodies (ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were analyzed with hematoxylin and eosin (HE) staining and immunocomplex (IC) assay. Results Urinary protein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0.05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group (P<0.05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0.05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0.05). Levels of IFN-γ and IL-4 in serum samples of the intervention group were decreased as compared with those of the model group (P<0.05). HE staining and immunofluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney immune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which alleviates and reverses the lupus-like nephritis-induced pathological damages in mice. Key words: Bivalent antibody; CD80; Co-stimulatory signals; Lupus nephritis; Pathological damage
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