problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl12470problendo-12470Research ArticleКлиническая эндокринологияClinical endocrinologyРоль генов системы HLA: от аутоиммунных заболеваний до COVID-19The role of HLA genes: from autoimmune diseases to COVID-19https://orcid.org/0000-0002-8520-8702ТрошинаЕкатерина АнатольевнаTroshinaEkaterina A.

д.м.н., профессор, член-корреспондент РАН; ORCID: 0000-0002-8520-8702; eLibrary SPIN: 8821-8990

Москва

MD, PhD, Professor; ORCID: 0000-0002-8520-8702; eLibrary SPIN: 8821-8990

Moscow

troshina@inbox.ruhttps://orcid.org/0000-0002-8771-8300ЮкинаМарина ЮрьевнаYukinaMarina Yu.

к.м.н.; ORCID: 0000-0002-8771-8300; eLibrary SPIN: 4963-8340

117036 Москва, ул. Дмитрия Ульянова, д. 11

MD, PhD; ORCID: 0000-0002-8771-8300; eLibrary SPIN: 4963-8340

11 Dm. Ulyanova street, 117036 Moscow

kuronova@yandex.ruhttps://orcid.org/0000-0001-6876-3336НуралиеваНурана ФейзуллаевнаNuralievaNurana F.

ORCID: 0000-0001-6876-3336; eLibrary SPIN: 7373-2602

Москва

ORCID: 0000-0001-6876-3336; eLibrary SPIN: 7373-2602

Moscow

Dr.NuralievaNF@yandex.ruhttps://orcid.org/0000-0002-9717-9742МокрышеваНаталья ГеоргиевнаMokryshevaNatalia G.

д.м.н., профессор, член-корреспондент РАН; ORCID: 0000-0002-9717-9742; eLibrary SPIN: 5624-3875

Москва

MD, PhD, Professor; ORCID: 0000-0002-9717-9742; eLibrary SPIN: 5624-3875

Moscow

nm70@mail.ruНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian Federation202001092020664915Copyright © Трошина Е.А., Юкина М.Ю., Нуралиева Н.Ф., Мокрышева Н.Г., 20202020Трошина Е.А., Юкина М.Ю., Нуралиева Н.Ф., Мокрышева Н.Г.Troshina E.A., Yukina M.Y., Nuralieva N.F., Mokrysheva N.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/12470

Гены системы HLA (Human Leukocyte Antigen) играют важную роль в нормальном функционировании иммунной системы. Различают три класса генов: I, II и III. Функция молекул HLA I класса заключается в презентации на поверхности клетки антигенов пептидов из цитоплазмы Т-лимфоцитам, а II класса — в презентации антигенов пептидов из внеклеточного пространства. В классическом представлении патологическая активация иммунной системы у пациентов с генетической предрасположенностью может приводить к развитию аутоиммунных заболеваний. Однако в последнее время рассматривается влияние этой системы и на развитие неаутоиммунных заболеваний, в том числе на их тяжесть и прогноз. Кроме того, молекулы HLA обеспечивают презентацию различных возбудителей инфекционных заболеваний. В связи с чем локусы главного комплекса гистосовместимости могут рассматриваться как кандидаты для определения генетической предрасположенности как к самим инфекционным заболеваниям, так и определять их течение. В данном обзоре выдвигается гипотеза, что определенные варианты генов HLA могут обуславливать формирование «цитокинового шторма» у пациентов с COVID-19. Выявление группы пациентов с особенными генетическими вариациями, обуславливающими нарушения иммунной толерантности и гиперактивный ответ на фоне вирусной инфекции, поможет оптимизировать алгоритм профилактики заболевания и лечения таких больных и, как следствие, ослабить напряженность эпидемиологической ситуации.

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.

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The authors declare that there are no conflicts of interest present.