mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EOH-3364mimmun-3364Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВЛИЯНИЕ ПОЛИМОРФИЗМА HLA II КЛАССА НА ВОСПРИИМЧИВОСТЬ К ИНФЕКЦИИ SARS-COV-2 И ТЯЖЕСТЬ ПРОТЕКАНИЯ ИНФЕКЦИОННОГО ПРОЦЕССАEFFECT OF HLA CLASS II POLYMORPHISM ON SUSCEPTIBILITY TO SARS-COV-2 INFECTION AND SEVERITY OF THE INFECTION PROCESShttps://orcid.org/0000-0001-5898-950XШевченкоА. В.ShevchenkoA. V.shalla64@mail.ruhttps://orcid.org/0000-0001-7385-6270КоненковВ. И.KonenkovV. I.vikonenkov@gmail.comhttps://orcid.org/0000-0001-7290-1631ПрокофьевВ. Ф.ProkofievV. F.vprok@ngs.ruhttps://orcid.org/0000-0002-0423-5021КарасеваА. А.KarasevaA. A.Sas96@bk.ruhttps://orcid.org/0000-0001-7875-1566АфанасьеваА. Д.AfanasevaA. D.alena.dmytryevna@yandex.ruhttps://orcid.org/0000-0003-1348-0253ЛогвиненкоИ. И.LogvinenkoI. I.111157@mail.ruНаучно-исследовательский институт клинической и экспериментальной лимфологии – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Российская ФедерацияРоссияResearch Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL- Branch of IC&G SB RAS), Novosibirsk, Russian FederationRussian FederationНаучно-исследовательский институт терапии и профилактической медицины - филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», г. Новосибирск, Российская ФедерацияРоссияResearch Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IIPM - Branch of IC&G SB RAS), Novosibirsk, Russian FederationRussian Federation20190502202600Online First3364Copyright © Шевченко А.В., Коненков В.И., Прокофьев В.Ф., Карасева А.А., Афанасьева А.Д., Логвиненко И.И., 20192019Шевченко А.В., Коненков В.И., Прокофьев В.Ф., Карасева А.А., Афанасьева А.Д., Логвиненко И.И.Shevchenko A.V., Konenkov V.I., Prokofiev V.F., Karaseva A.A., Afanaseva A.D., Logvinenko I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/3364

Ряд исследований выявил связь генетических вариантов главного комплекса гистосовместимости, регулирущего экспрессию молекул человеческого лейкоцитарного антигена (HLA) с особенностями протекания короновирусной инфекции (COVID-19). Цель - определение связи между HLA полиморфизмом и COVID -19, а также тяжестью течения инфекционного процесса у пациентов Западно-Сибирского региона России. Обследовано 260 пациентов после двух месяцев реконвалесценции с диагнозом COVID-19. В группу сравнения вошли 372 жителя Новосибирской области. Проводилось генотипирование аллелей и групп аллелей с использованием тест-систем ДНК-технология, Москва. При статистической обработке результатов использовался пакет IBM SPSS Statistics 23 и Arlequin 3.5.2. Выявлено увеличение частоты DRB1*15; DQA1*01:02 и снижение частот DRB1*03; DQA1*01:03 и DQB1*05:03 в группе пациентов с COVID-19 относительно контрольной группы. После внесения поправки Бонферрони достоверные различия сохранились только для DQA1*01:02. Выявлено три гаплотипа, достоверно различающиеся между группами без поправки на множественность. Частота DRB1*07,15; DQA1*01:02,0201 и DQB1*02,06:02-08 генотипов преобладала у пациентов с COVID-19 относительно группы сравнения. Cочетания генотипов DRB1*07,15-DQB1*02,06:02-08; DRB1*07,15-DQA1*01:02,02:01-DQB1*02,06:02-08; DQA1*01:02,02:01-DQB1*02,06-02-08 преобладали в группе переболевших относительно контрольной группы. Генотипы DRB1*07,11; DRB1*11,15 и сочетания генотипов DRB1*11,15-DQA1*01:02,05:01-DQB1*03:01,06:02-08; DRB1*07,11-DQA1*02:01,05:01; DRB1*11,15-DQA1*01:02,05:01; DRB1*11,15-DQB1*03:01,06:02-08 присутствовали только у пациентов с тяжелой формой течения болезни и полностью отсутствовали у пациентов с легким течением. Частоты DRB1*11; DRB1*07,11 и DRB1*07,11-DQA1*02:01,05:01 были выше в объединённой группе пациентов с тяжелым плюс средним течением болезни относительно группы пациентов с легким течением заболевания. Полученные результаты вносят определенный вклад в выяснение ассоциации полиморфизма генов HLA с COVID-19 не только у населения Западной Сибири, но и Российской Федерации в целом. Необходимы дальнейшие исследования с увеличением размеров выборки, что, вероятно, позволит преодолеть порог значимости при введении поправок на множественность аллелей.

The conducted studies have revealed the potential role of genetic variants of the main histocompatibility complex, which regulates the expression of human leukocyte antigen molecules (HLA) in the course of coronavirus infection (COVID-19). The aim: The aim - determine the relationship between HLA polymorphism and COVID-19, as well as the severity of the infection process in patients of the West Siberian of Russia. 260 patients with COVID-19 were examined after two months of convalescence. The comparison group included 372 residents of the Novosibirsk region. Genotyping alleles and alleles groups was performed using DNA-technology test-systems, Moscow. The IBM SPSS Statistics 23 and Arlequin 3.5.2 were used for statistical processing. An increase DRB1*15; DQA1*01:02 and decrease DRB1*03; DQA1*01:03; DQB1*05:03 frequency were detected in the COVID-19 patient relative control group. Differences remained only for DQA1*01:02 after Bonferroni correction. Three haplotypes were identified, which differed between the groups without Bonferroni correction. DRB1*07,15; DQA1*01:02,0201 and DQB1*02,06:02-08 frequency prevailed in patients relative control group. DRB1*07,15-DQB1*02,06:02-08; DQA1*01:02,02:01-DQB1*02,06-02-08 and DRB1*07,15-DQA1*01:02,02:01-DQB1*02,06:02-08 combinations prevailed in COVID-19 patients relative control group. Genotypes DRB1*07,11; DRB1*11,15 and combinations DRB1*07,11-DQA1*02:01,05:01; DRB1*11,15-DQA1*01:02,05:01; DRB1*11,15-DQB1*03:01,06:02-08, DRB1*11,15-DQA1*01:02,05:01-DQB1*03:01,06:02-08 were present only in patients with severe disease. DRB1*11, DRB1*07,11 and DRB1*07,11-DQA1*02:01,05:01 were higher in the combined group with severe plus moderate severity of the disease relative to the group of patients with mild disease. These results obtained make a definite contribution to clarifying the role of HLA- polymorphism in COVID-19 not only in Western Siberia, but also in the Russian Federation as a whole. Researches are needed with an increase in sample size, which is likely to overcome the threshold of significance when correcting for the multiplicity of alleles.

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