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[人类白细胞抗原基因的作用:从自身免疫性疾病到2019冠状病毒病]

[The role of HLA genes: from autoimmune diseases to COVID-19].

作者信息

Troshina Ekaterina A, Yukina Marina Yu, Nuralieva Nurana F, Mokrysheva Natalia G

机构信息

Endocrinology Research Centre.

出版信息

Probl Endokrinol (Mosk). 2020 Sep 1;66(4):9-15. doi: 10.14341/probl12470.

Abstract

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II - to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm» in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.

摘要

人类白细胞抗原(HLA)系统的基因在免疫系统的正常运作中起着至关重要的作用。该系统有三类基因:I类、II类和III类。I类HLA分子的功能是将细胞质中的肽抗原呈递给细胞表面的T淋巴细胞,而II类HLA分子则是将细胞外空间的肽抗原呈递给T淋巴细胞。传统观点认为,具有遗传易感性的患者免疫系统的病理性激活可导致自身免疫性疾病的发生。然而,最近人们开始关注该系统对非自身免疫性疾病的发生、严重程度及预后的影响。此外,HLA分子还能呈递各种感染因子。因此,主要组织相容性复合体的基因座可被视为决定对传染病及其病程遗传易感性的候选基因。本综述推测,HLA基因的特定变体可能导致COVID-19患者形成“细胞因子风暴”。识别出一组具有特定基因变异、在病毒感染时导致免疫耐受破坏和高反应性的患者,将有助于优化此类患者的疾病预防和治疗方案,从而减轻疫情的严重程度。

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