Anti-ANX A1 Antibody Therapy in MRL/lpr Murine Model of Systemic Lupus Erythematosus

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2021-07-28 DOI:10.1007/s00005-021-00624-7
Silvya Bradyanova, Nikolina Mihaylova, Petroslav Chipinski, Yordan Manassiev, Melinda Herbáth, Dobroslav Kyurkchiev, József Prechl, Andrey I. Tchorbanov
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Abstract

Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by dysfunction of immune regulation, overproduction of inflammatory cytokines and attack on normal tissues by self-reactive cells and antibodies. The main role in the pathogenesis plays the autoreactive tandem of B-T cells, responsible for lupus progression and acceleration. Both activated B and T cells express a phospholipid binding protein Annexin A1 and abnormal levels of the protein were found in murine and human autoimmune syndromes, potentiating its role as a therapeutic target. Here, using anti-annexin A1 antibody we explore its property to modulate the autoimmune response in MRL/lpr mouse model of lupus. Anti-ANX A1 antibody was tested in vitro using spleen cells from MRL/lpr mice to determine the effect on lymphocyte activation, plasma cells differentiation, apoptosis and proliferation by flow cytometry and ELISpot assays. Subsequently, several groups of young (disease-free) and old (sick) MRL/lpr mice were treated with the antibody to determine the levels of panel auto-antibodies and cytokines, T cell arrest and migration. Treatment of splenocytes with anti-ANX A1 antibody inhibited T-cell activation and proliferation, suppressed anti-dsDNA antibody-producing plasma cells and affected B cell apoptosis. Administration of the antibody to MRL/lpr mice resulted to decreased autoantibody levels to various lupus antigens, suppressed T cell migration from lymph nodes and increased the levels of IL4 mRNA compared to the control group. Anti-ANX A1 antibody therapy suppresses B and T cell over-activation and down- modulates disease activity.

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抗anx A1抗体治疗系统性红斑狼疮MRL/lpr小鼠模型
系统性红斑狼疮(SLE)是一种严重的自身免疫性疾病,其特征是免疫调节功能障碍、炎性细胞因子过度产生以及自身反应细胞和抗体攻击正常组织。发病机制中的主要作用是B-T细胞的自身反应串联,负责狼疮的进展和加速。活化的B细胞和T细胞都表达磷脂结合蛋白Annexin A1,在小鼠和人类自身免疫综合征中发现该蛋白水平异常,增强了其作为治疗靶点的作用。在这里,使用抗膜联蛋白A1抗体,我们探索了其在狼疮MRL/lpr小鼠模型中调节自身免疫反应的特性。使用来自MRL/lpr小鼠的脾细胞在体外测试抗ANX A1抗体,以通过流式细胞术和ELISpot测定来确定其对淋巴细胞活化、浆细胞分化、细胞凋亡和增殖的影响。随后,用该抗体治疗几组年轻(无病)和老年(患病)MRL/lpr小鼠,以确定群体自身抗体和细胞因子的水平、T细胞停滞和迁移。用抗ANX A1抗体处理脾细胞抑制T细胞活化和增殖,抑制产生抗dsDNA抗体的浆细胞并影响B细胞凋亡。与对照组相比,对MRL/lpr小鼠施用抗体导致对各种狼疮抗原的自身抗体水平降低,抑制T细胞从淋巴结迁移,并增加IL4mRNA水平。抗ANX A1抗体治疗抑制B和T细胞过度活化并下调疾病活性。
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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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