Role of class I HLA (G, E, and C) expression in early reproductive losses


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Abstract

In 50-80% of cases, immunological factors are the main causes of early reproductive losses with a normal karyotype of the fetus, as the immune system has been proven to play one of the major roles in the processes of fertilization, implantation, and placentation. The basis of whole-body immunity is the system of HLA (Human Leukocyte Antigen), a highly polymorphic locus containing the genes, the products of which control the interaction of the body’s all immunocompetent cells, recognize their own and foreign (including altered own) cells, trigger and implement an immune response. The review presents data on class I HLA genes that have central functions in antigen processing and presentation, inhibit a NK cell receptor, which leads to a decrease in the immune response at the mother-fetus interface, and provide immune tolerance to the fetus. HLA-E and HLA-C expression is noted to have a special role in the successful occurrence of pregnancy. HLA-G is expressed by the cells of cytotrophoblast, placenta, and amnion in a tissue-specific manner. Three meta-analyses have shown an association between HLA-G 14-bp ins polymorphism and recurrent miscarriage (especially in women with a history of three or more spontaneous miscarriages). Class I HLA genes, as a modulator of the immune system, have a protective effect at all implantation stages.

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About the authors

Margarita O. Bakleicheva

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Email: bakleicheva@gmail.com
junior research scientist

Olesya N. Bespalova

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

MD, deputy director for research

Tatiana E. Ivashchenko

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

PhD, D.Sc., leading researcher of Department of Genomic medicine, of Biological Sciences, Professor

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