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Monoclonal antibody therapy that targets phospholipid-binding protein delays lupus activity in MRL/lpr mice.
Scandinavian Journal of Immunology ( IF 3.7 ) Pub Date : 2020-06-13 , DOI: 10.1111/sji.12915
Nikolina Mihaylova 1 , Silviya Bradyanova 1 , Petroslav Chipinski 1 , Stela Chausheva 1 , Dobroslav Kyurkchiev 2 , Andrey I Tchorbanov 1, 3
Affiliation  

Systemic lupus erythematosus is an autoimmune syndrome characterized by the development of autoantibodies to a wide range of antigens. Together with B cells, respective self‐reactive T cells have an important contribution in disease progression as being responsible for inflammatory cytokines secretion, B cell activation and promoting amplification of the autoimmune response. Annexin A1 is expressed by many cell types and binds to phospholipids in a Ca2+‐dependent manner. Abnormal expression of annexin A1 was found on activated B and T cells in both murine and human autoimmunity suggesting its potential role as a therapeutic target. In the present study, we have investigated the possibility to suppress autoimmune manifestation in spontaneous mouse model of lupus using anti‐annexin A1 antibody. Groups of lupus‐prone MRL/lpr mice were treated with the anti‐annexin A1 monoclonal antibody, and the disease activity and survival of the animals were following up. Flow cytometry, ELISA assays, and histological and immunofluorescence kidney analyses were used to determine the levels of Annexin A1 expression, cytokines, anti‐dsDNA antibodies and kidney injuries. The administration of this monoclonal antibody to MRL/lpr mice resulted in suppression of IgG anti‐dsDNA antibody production, modulated IL‐10 secretion, decreased disease activity and prolonged survival compared with the control group.

中文翻译:

靶向磷脂结合蛋白的单克隆抗体疗法可延缓MRL / lpr小鼠的狼疮活性。

系统性红斑狼疮是一种自身免疫综合征,其特征是针对多种抗原的自身抗体的发展。各自的自我反应性T细胞与B细胞一起,在疾病的发展中起着重要的作用,它负责炎症性细胞因子的分泌,B细胞的活化并促进自身免疫应答的扩增。Annexin A1由许多细胞类型表达,并与Ca 2+中的磷脂结合依赖方式。在鼠和人自身免疫中均在活化的B和T细胞上发现了膜联蛋白A1的异常表达,表明其可能作为治疗靶标。在本研究中,我们研究了使用抗安心毒素A1抗体抑制狼疮自发小鼠模型中自身免疫表现的可能性。用抗抗annexin A1单克隆抗体治疗易患狼疮的MRL / lpr小鼠组,并跟踪其疾病活动性和存活率。使用流式细胞仪,ELISA分析以及组织学和免疫荧光肾分析来确定膜联蛋白A1表达,细胞因子,抗dsDNA抗体和肾脏损伤的水平。向MRL / lpr小鼠施用这种单克隆抗体可抑制IgG抗dsDNA抗体的产生,
更新日期:2020-08-18
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