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中间丝相关蛋白作为自身免疫性疾病的抗原靶点:全面综述。

Vimentin as antigenic target in autoimmunity: A comprehensive review.

机构信息

Laboratory for Diagnostics of Autoimmune Diseases, Center for Molecular Medicine, Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation.

Laboratory for Diagnostics of Autoimmune Diseases, Center for Molecular Medicine, Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation.

出版信息

Autoimmun Rev. 2018 Sep;17(9):926-934. doi: 10.1016/j.autrev.2018.04.004. Epub 2018 Jul 17.

Abstract

Vimentin is a protein of intermediate filament family, which is expressed in all mesenchymal cells. Vimentin plays a key role in the physiology of the cell, cellular interactions and the functioning of the immune system. Post-translationally modified and native forms of vimentin are involved in the pathogenesis of inflammation and many autoimmune diseases: rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, antiphospholipid syndrome, Crohn's disease, ankylosing spondyloarthritis and idiopathic pulmonary fibrosis. Modifications of the protein lead to the formation of antigenic epitopes and, as a result, to the synthesis of antibodies. Citrullinated, carbamylated and acetylated forms of vimentin participate in the pathogenesis of RA, and antibodies against them serve as diagnostic and prognostic markers of the disease. Epitopes of native vimentin are antigenic in the group of HLA-DRB1*0301 positive patients with sarcoidosis. In addition, vimentin takes part in pathogenesis of tubulointerstitial inflammation and glomerulonephritis in lupus. In antiphospholipid syndrome interactions of vimentin and cardiolipin on the surface of apoptotic cells lead to the formation of an immunogenic complex. Antibodies against vimentin/cardiolipin complex are involved in the mechanism of thrombogenesis and serve to identify patients seronegative for antibodies to cardiolipin and ß2glycoprotein-I with the clinical features. Post-translationally modified form of the protein is citrullinated and MMP-degraded vimentin, which was found in serum of patients with Crohn's disease and ankylosing spondyloarthritis.

摘要

波形蛋白是中间丝家族的一种蛋白,存在于所有间质细胞中。波形蛋白在细胞生理学、细胞间相互作用和免疫系统功能中起着关键作用。翻译后修饰和天然形式的波形蛋白参与炎症和许多自身免疫性疾病的发病机制:类风湿关节炎、结节病、系统性红斑狼疮、抗磷脂综合征、克罗恩病、强直性脊柱炎和特发性肺纤维化。蛋白质的修饰导致抗原表位的形成,从而导致抗体的合成。瓜氨酸化、氨甲酰化和乙酰化形式的波形蛋白参与 RA 的发病机制,针对它们的抗体可作为疾病的诊断和预后标志物。天然波形蛋白的表位在结节病 HLA-DRB1*0301 阳性患者中具有抗原性。此外,波形蛋白参与狼疮性小管间质性炎症和肾小球肾炎的发病机制。在抗磷脂综合征中,波形蛋白与心磷脂在凋亡细胞表面的相互作用导致免疫原性复合物的形成。针对波形蛋白/心磷脂复合物的抗体参与血栓形成机制,并有助于识别具有临床特征的抗心磷脂抗体和β2糖蛋白-I 血清阴性患者。在克罗恩病和强直性脊柱炎患者的血清中发现了翻译后修饰形式的瓜氨酸化和 MMP 降解的波形蛋白。

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