mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-SOR-2155mimmun-2155Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИзучение связи полиморфизма гена HLA-G, внутриматочной инфекции и невынашивания беременности у женщинStudy of relationships between HLA-G gene polymorphism, intrauterine infection and recurrent miscarriage in womenhttps://orcid.org/0000-0001-5870-7584ГордееваЛ. А.GordeevaL. A.

к.б.н., ведущий научный сотрудник лаборатории иммуногенетики,

650065, г. Кемерово, Ленинградский пр., 10

PhD (Biology), Leading Research Associate, Laboratory of Immunogenetics, 

650065, Kemerovo, Leningradsky ave., 10

ihe@kemtel.ru

gorsib@rambler.ruВоронинаЕ. Н.VoroninaE. N.

к.б.н., научный сотрудник лаборатории фармакогеномики,

г. Новосибирск

PhD (Biology), Research Associate, Laboratory of Pharmacogenomics, 

Novosibirsk

voronina_l@mail.ruПоленокЕ. Г.PolenokE. G.

к.фарм.н., ведущий научный сотрудник лаборатории иммунохимии,

г. Кемерово

PhD (Pharmacy), Leading Research Associate, Laboratory of Immunochemistry,

Kemerovo

egpolenok@mail.ruМунС. А.MunS. A.

к.м.н., старший научный сотрудник лаборатории иммуногенетики,

 г. Кемерово

PhD (Medicine), Senior Research Associate, Laboratory of Immunogenetics,

Kemerovo

stellamun@yandex.ruНерсесянС. Л.NersesyanS. L.

врач-генетик медико-генетической консультации,

г. Кемерово

Geneticist, Genetic Counseling Center, 

Kemerovo

wilsa2007@rambler.ruОленниковаР. В.OlennikovaR. V.

врач-генетик медико-генетической консультации,

г. Кемерово

Geneticist, Genetic Counseling Center,

Kemerovo

olennri@yandex.ruФилипенкоМ. Л.FilipenkoM. L.

к.б.н., заведующий лабораторией фармакогеномики,

г. Новосибирск

PhD (Biology), Head, Laboratory of Pharmacogenomics,

Novosibirsk

max@niboch.nsc.ruГлушковА. Н.GlushkovA. N.

 д.м.н., заместитель директора, 

 г. Кемерово

PhD, MD (Medicine), Deputy Director,

Kemerovo

ihe@list.ruФедеральный исследовательский центр угля и углехимии Сибирского отделения Российской академии наук (Институт экологии человека СО РАН)РоссияFederal Research Center of Coal and Coal Chemistry, Siberian Branch, Russian Academy of Sciences (Institute of Human Ecology, SB RAS)Russian FederationФГБУН «Институт химической биологии и фундаментальной медицины» Сибирского отделения Российской академии наукRussian FederationInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of SciencesRussian FederationГАУЗ «Кемеровская областная клиническая больница»Russian FederationKemerovo Regional Clinical HospitalRussian FederationФГБУН «Институт химической биологии и фундаментальной медицины» Сибирского отделения Российской академии наукRussian FederationInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of SciencesRussian Federation202124042021232369380Copyright © Гордеева Л.А., Воронина Е.Н., Поленок Е.Г., Мун С.А., Нерсесян С.Л., Оленникова Р.В., Филипенко М.Л., Глушков А.Н., 20212021Гордеева Л.А., Воронина Е.Н., Поленок Е.Г., Мун С.А., Нерсесян С.Л., Оленникова Р.В., Филипенко М.Л., Глушков А.Н.Gordeeva L.A., Voronina E.N., Polenok E.G., Mun S.A., Nersesyan S.L., Olennikova R.V., Filipenko M.L., Glushkov A.N.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/2155

Изучали связь полиморфизма гена HLA-G (rs41551813, rs12722477 и rs41557518), внутриматочной инфекции и невынашивания беременности у женщин. Исследуемую группу (НБ) составили 180 женщин с невынашиванием беременности, определяемой как два и более повторяющихся самопроизвольных выкидыша (min = 2; max = 8) до 20 недель беременности. На момент обследования женщины были не беременными и наблюдались в медико-генетической консультации г. Кемерово. Каждая женщина прошла гинекологическое обследование. Из исследования были исключены женщины с медицинскими абортами, родами и внематочными беременностями, с сахарным диабетом. Для исключения других известных причин самопроизвольного выкидыша были проведены ультразвуковое исследование органов малого таза и кариотипирование женщины и мужчины. Средний возраст женщин составил 29,6±4,8 (SD) лет. Группа сравнения (контроль) включала 408 здоровых и фертильных женщин. Критериями включения в исследование для них были роды 1-2 здоровых детей. Средний возраст женщин составил 26,8±5,2 (SD) лет. Влияние инфекционного фактора анализировали на основании лабораторных тестов: микроскопического исследования (для выявления бактериального вагиноза и вульво-вагинального кандидоза); иммуноферментного анализа и полимеразно-цепной реакции (для выявления генитального герпеса, цитомегаловируса, вируса папиломы человека типа 16/18; Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum и Gardnerella vaginalis; и Trichomonas vaginalis. Данные были получены из медицинских карт обследуемых женщин. Все женщины дали письменное информированное согласие на участие в исследовании. Типирование полиморфизма Thr31Ser (rs41551813, HLA-G*01:03) в экзоне 2, Leu110Ile (rs12722477, HLA-G*01:04) и 1597 delС (rs41557518, HLA-G*01:05N) в экзоне 3 гена HLA-G проводили методом асимметричной ПЦР в режиме реального времени. Как показало исследование, у обследуемых женщин внутриматочная инфекция не являлась самостоятельно значимым фактором риска НБ (p = 0,30). Обнаружено, что аллель 110 Ile (HLA-G*01:04) являлся фактором риска НБ как у женщин с внутриматочной инфекцией (ORa = 4,50 [2,41-8,38], p = 2,09e-06), так и у женщин без инфекции (ORa = 2,46 [1,44-4,21], p = 0,0009). Выявлено совместное влияние генетического и инфекционного факторов с риском НБ у женщин (ORa+f = 3,50 [2,01-6,09], p = 8,78e-06). Наши результаты могут быть полезны в понимании молекулярных механизмов иммунных нарушений в системе мать-плод и при выборе тактики ведения и лечения женщин с НБ. 

The relationship between the HLA-G gene polymorphism (rs41551813, rs12722477, rs41557518), intrauterine infection and recurrent miscarriage (RM) in women were studied. The case group consisted of 180 patients with RM, defined as two or more consecutive miscarriages (min = 2; max = 8) at up to 20 weeks of gestation, and with clinically confirmed pregnancies and non-viable fetuses. At the time of examination. the women were enrolled from the Genetic Counseling Center at the Kemerovo Regional Clinical Hospital, Kemerovo, Russia, and were not pregnant. Each patient underwent a gynecological examination. We excluded women with a history of medical abortion, birth, and ectopic pregnancies. In addition, we excluded women with endocrine (e.g. diabetes) disorders. To exclude other known causes of spontaneous abortion, the following tests were performed: ultrasound examination of pelvic organs, and karyotyping in women and men. The women’s mean age in the RM group, was 29.6±4.8 (SD) years. The control group comprised 408 fertile women. These women didn’t have a history of spontaneous abortion, or a family history of congenital malformations. They have born, at least, 1-2 healthy children. Women’s mean age at birth of last child was 26.8±5.2 (SD) years. Influence of the intrauterine infection was analyzed on the basis of laboratory tests. Diagnostics of bacterial vaginosis and vulvo-vaginal candidiasis by microscopic examination was conducted. Viral agent infections (herpes simplex virus type 2, cytomegalovirus, human papilloma virus type 16/18), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis and Trichomonas vaginalis were detected by enzyme-linked immunoassay and polymerase chain reaction (PCR). The data were obtained from the medical cards of the surveyed women. All the women gave a written informed consent before participating in the study. Typing of polymorphisms of Thr31Ser (rs41551813, HLA-G*01:03) in exon 2, Leu110Ile (rs12722477, HLA-G*01:04) and 1597 delС (rs41557518, HLA-G*01:05N) in exon 3 HLA-G genes were performed by realtime PCR followed by melting analysis. The study showed that the intrauterine infection was not a risk factor for RM (p = 0.30) in the examined women. It was found that the 110 Ile allele (HLA-G *01:04) was a risk factor for RM both in women with intrauterine infection [ORa = 4.50 (2.41-8.38), p = 2.09e-06], and in women without infection [ORa = 2.46 (1.44-4.21), p = 0.0009]. The cooperative influence of genetic and infections factors with the risk of RM in women was revealed [ORa+f = 3.50 (2.01-6.09), p = 8.78e-06]. Our results will be useful in understanding the molecular mechanisms of immune disorders in fetomaternal interface, and for choosing the strategy of management and treatment in women with RM. 

генетический полиморфизмHLA-Gневынашивание беременностиgenetic polymorphismHLA-Grecurrent miscarriageReferencesАленичев А.С., Насыхова Ю.А., Иващенко Т.Э., Баранов В.С. Характеристика генетической структуры популяции Северо-западного региона РФ по гену HLA-G // Экологическая генетика, 2014. Т. XII. № 2. С. 74-80.Alenichev A.S., Nasykhova Yu.A., Ivashchenko T.E., Baranov V.S. Population genetic structure of HLA-G gene in North-west Region of Russian Federation. Ekologicheskaya genetika = Ecological Genetics, 2014, Vol. XII, no. 2, pp. 47-80. (In Russ.)Вавилин В.А., Часовникова О.Б., Ляхович В.В., Гавалов С.М., Рябова О.А. Генетический полиморфизм глутатион-S-трансферазы M1 и T1 у детей, больных бронхиальной астмой // Вопросы медицинской химии, 2000. Т. 46, № 4. C. 388-397.Vavilin V.A., Chasovnikova О.B., Lyakhovich V.V., Gavalov S.M., Ryabova O.A. Genetic polymorphisms of glutathione S-transferase Ml and T1 in asthmatic childrens. Voprosy meditsinskoy khimii = Medical Chemistry Issues, 2000, Vol. 11, no. 6, pp. 541- 548. (In Russ.)Герлинская Л.А., Варлачев А.В., Кротов Г.И., Концевая Г.В., Мошкин М.П. Иммуногенетический диалог матери и эмбрионов как фактор становления иммунного статуса потомков // Вавиловский журнал генетики и селекции, 2018. Т. 22, № 8. С. 1009-1019.Gerlinskaya L.A., Varlachev A.V., Krotov G.I., Kontsevaya G.V., Moshkin M.P. Mother-fetus immunogenetic dialogue as a factor of progeny immune system development. Vavilovskiy zhurnal genetiki i selektsii = Vavilov Journal of Genetics and Breeding, 2018, Vol. 22, no. 8, pp. 1009-1019. (In Russ.)Черных Е.Р., Селедцова Н.В., Леплина О.Ю., Тихонова М.А., Тыринова Т.В., Курганова Е.В., Хонина Н.А., Останин А.А., Пасман Н.М. Дендритные клетки как возможные регуляторы иммунной перестройки при беременности // Медицинская иммунология, 2009. Т. 11, № 6. С. 541-548. doi: 10.15789/1563-0625-2009-6-541-548.Chernykh E.R., Seledtsova N.V., Leplina O.Yu., Tikhonova M.A., Tyrinova T.V., Kurganova E.V., Khonina N.A., Ostanin A.A., Pasman N.M. Dendritic cells as possible regulators of immune reorganization in pregnancy. Meditsinskaya immunologiya = Medical Immunology (Russia), 2009, Vol. 11, no. 6, pp. 541- 548. (In Russ.) doi: 10.15789/1563-0625-2009-6-541-548.Aldrich C.L., Stephenson M.D., Karrison T., Odem R.R., Branch D.W., Scott J.R., Schreiber J.R., Ober C. HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. Mol. Hum. Reprod., 2001, Vol. 7, no. 12, pp. 1167-1172.Aldrich C.L., Stephenson M.D., Karrison T., Odem R.R., Branch D.W., Scott J.R., Schreiber J.R., Ober C. HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. Mol. Hum. Reprod., 2001, Vol. 7, no. 12, pp. 1167-1172.Alegre E., Díaz-Lagares A., Lemaoult J., López-Moratalla N., Carosella E.D., González A. Maternal antigen presenting cells are a source of plasmatic HLA-G during pregnancy: longitudinal study during pregnancy. Hum. Immunol., 2007, Vol. 68, no. 8, pp. 661-667.Alegre E., Díaz-Lagares A., Lemaoult J., López-Moratalla N., Carosella E.D., González A. Maternal antigen presenting cells are a source of plasmatic HLA-G during pregnancy: longitudinal study during pregnancy. Hum. Immunol., 2007, Vol. 68, no. 8, pp. 661-667.Amiot L., Vu N., Samson M. Immunomodulatory properties of HLA-G in infectious diseases. J. Immunol. Res., 2014, Vol. 2014, 298569. doi: 10.1155/2014/298569.Amiot L., Vu N., Samson M. Immunomodulatory properties of HLA-G in infectious diseases. J. Immunol. Res., 2014, Vol. 2014, 298569. doi: 10.1155/2014/298569.Carlini F., Picard C., Garulli C., Piquemal D., Roubertoux P., Chiaroni J., Chanez P., Gras D., Di Cristofaro J. Bronchial epithelial cells from asthmatic patients display less functional HLA-G isoform expression. Front. Immunol., 2017, Vol. 8, 6. doi: 10.3389/fimmu.2017.00006.Carlini F., Picard C., Garulli C., Piquemal D., Roubertoux P., Chiaroni J., Chanez P., Gras D., Di Cristofaro J. Bronchial epithelial cells from asthmatic patients display less functional HLA-G isoform expression. Front. Immunol., 2017, Vol. 8, 6. doi: 10.3389/fimmu.2017.00006.Carosella E.D., Gregori S., LeMaoult J. The tolerogenic interplay(s) among HLA-G, myeloid APCs, and regulatory cells. Blood., 2011, Vol. 118, no. 25, pp. 6499-6505.Carosella E.D., Gregori S., LeMaoult J. The tolerogenic interplay(s) among HLA-G, myeloid APCs, and regulatory cells. Blood., 2011, Vol. 118, no. 25, pp. 6499-6505.Castelli E.C., Mendes-Junior C.T., Deghaide N.H.S., de Albuquerque R.S., Muniz Y.C.N., Simões R.T., Carosella E.D., Moreau P., Donadi E.A. The genetic structure of 3’untranslated region of the HLA-G gene: polymorphisms and haplotypes. Genes Immun., 2010, Vol. 11, no. 2, pp. 134-141.Castelli E.C., Mendes-Junior C.T., Deghaide N.H.S., de Albuquerque R.S., Muniz Y.C.N., Simões R.T., Carosella E.D., Moreau P., Donadi E.A. The genetic structure of 3’untranslated region of the HLA-G gene: polymorphisms and haplotypes. Genes Immun., 2010, Vol. 11, no. 2, pp. 134-141.Celik A.A., Simper G.S., Huyton T., Blasczyk R., Bade-Döding C. HLA-G mediated immune regulation is impaired by a single amino acid exchange in the alpha 2 domain. Hum. Immunol., 2018, Vol. 79, no. 6, pp. 453-462.Celik A.A., Simper G.S., Huyton T., Blasczyk R., Bade-Döding C. HLA-G mediated immune regulation is impaired by a single amino acid exchange in the alpha 2 domain. Hum. Immunol., 2018, Vol. 79, no. 6, pp. 453-462.Celsi F., Catamo E., Kleiner G., Tricarico P.M., Vuch J., Crovella S. HLA-G/C, miRNAs, and their role in HIV infection and replication. Biomed. Res. Int., 2013, Vol. 2013, 693643. doi: 10.1155/2013/693643.Celsi F., Catamo E., Kleiner G., Tricarico P.M., Vuch J., Crovella S. HLA-G/C, miRNAs, and their role in HIV infection and replication. Biomed. Res. Int., 2013, Vol. 2013, 693643. doi: 10.1155/2013/693643.Crespo Â.C., van der Zwan A., Ramalho-Santos J., Strominger J.L., Tilburgs T. Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections. J. Reprod. Immunol., 2017, Vol. 119, pp. 85-90.Crespo Â.C., van der Zwan A., Ramalho-Santos J., Strominger J.L., Tilburgs T. Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections. J. Reprod. Immunol., 2017, Vol. 119, pp. 85-90.CristofaroJ.D., Reynaud-Gaubert M.,Carlini F., Roubertoux P., LoundouA., Basire A., Frassati C., Thomas P., Gomez C., Picard C.HLA-G*01:04∼UTR3 recipient correlates with lower survival and higher frequency of chronic rejection after lung transplantation. Am. J. Transplant., 2015, Vol. 15, no. 9, pp. 2413-2420.CristofaroJ.D., Reynaud-Gaubert M.,Carlini F., Roubertoux P., LoundouA., Basire A., Frassati C., Thomas P., Gomez C., Picard C.HLA-G*01:04∼UTR3 recipient correlates with lower survival and higher frequency of chronic rejection after lung transplantation. Am. J. Transplant., 2015, Vol. 15, no. 9, pp. 2413-2420.Dahl M., Klitkou L., Christiansen O.B., Djurisic S., Piosik Z.M., Skovbo P., Møller. A.M., Steffensen R., HviidT.V.F. Human leukocyte antigen (HLA)-G during pregnancy part II: associations between maternal and fetal HLA-G genotypes and soluble HLA-G. Hum. Immunol., 2015, Vol. 76, no. 4, pp. 260-271.Dahl M., Klitkou L., Christiansen O.B., Djurisic S., Piosik Z.M., Skovbo P., Møller. A.M., Steffensen R., HviidT.V.F. Human leukocyte antigen (HLA)-G during pregnancy part II: associations between maternal and fetal HLA-G genotypes and soluble HLA-G. Hum. Immunol., 2015, Vol. 76, no. 4, pp. 260-271.d’Almeida T.C., Sadissou I., Sagbohan M., Milet J., Avokpaho E., Gineau L., Sabbagh A., Moutairou K., Donadi E.A, Favier B., Pennetier C., Baldet T., Moiroux N., Carosella E., Moreau P., Rouas-Freiss N, Cottrell G., Courtin D., Garcia A. High level of soluble human leukocyte antigen (HLA)-G at beginning of pregnancy as predictor of risk of malaria during infancy. Sci Rep., 2019, Vol. 9, no. 1, 9160. doi: 10.1038/s41598-019-45688-w.d’Almeida T.C., Sadissou I., Sagbohan M., Milet J., Avokpaho E., Gineau L., Sabbagh A., Moutairou K., Donadi E.A, Favier B., Pennetier C., Baldet T., Moiroux N., Carosella E., Moreau P., Rouas-Freiss N, Cottrell G., Courtin D., Garcia A. High level of soluble human leukocyte antigen (HLA)-G at beginning of pregnancy as predictor of risk of malaria during infancy. Sci Rep., 2019, Vol. 9, no. 1, 9160. doi: 10.1038/s41598-019-45688-w.di Cristofaro J., El Moujally D., Agnel A., Mazieres S., Cortey M., Basire A., Chiaroni J., Picard C. HLA-G haplotype structure shows good conservation between different populations and good correlation with high, normal and low soluble HLA-G expression. Hum Immunol., 2013, Vol. 74, no. 2, pp. 203-206.di Cristofaro J., El Moujally D., Agnel A., Mazieres S., Cortey M., Basire A., Chiaroni J., Picard C. HLA-G haplotype structure shows good conservation between different populations and good correlation with high, normal and low soluble HLA-G expression. Hum Immunol., 2013, Vol. 74, no. 2, pp. 203-206.Donadi E.A., Castelli E.C., Arnaiz-Villena A., Roger M., Rey D., Moreau P. Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association. Cell. Mol. Life Sci., 2011, Vol. 68, no. 3, pp. 369-395.Donadi E.A., Castelli E.C., Arnaiz-Villena A., Roger M., Rey D., Moreau P. Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association. Cell. Mol. Life Sci., 2011, Vol. 68, no. 3, pp. 369-395.Ferreira L.M.R., Meissner T.B., Tilburgs T., Strominger J.L. HLA-G: at the interface of maternal-fetal tolerance. Trends Immunol., 2017, Vol. 38, no. 4, pp. 272-286.Ferreira L.M.R., Meissner T.B., Tilburgs T., Strominger J.L. HLA-G: at the interface of maternal-fetal tolerance. Trends Immunol., 2017, Vol. 38, no. 4, pp. 272-286.Jucaud V., Ravindranath M.H., Terasaki P.I. Immunobiology of HLA class-Ib molecules in transplantation. SOJ Immunol., 2015, Vol. 3, no. 4, pp. 1-15.Jucaud V., Ravindranath M.H., Terasaki P.I. Immunobiology of HLA class-Ib molecules in transplantation. SOJ Immunol., 2015, Vol. 3, no. 4, pp. 1-15.Louvanto K., Roger M., Faucher M.C., Syrjänen K., Grenman S, Syrjänen S. HLA-G and vertical mother-tochild transmission of human papillomavirus infection. Hum. Immunol., 2018, Vol. 79, no. 6, pp. 471-476.Louvanto K., Roger M., Faucher M.C., Syrjänen K., Grenman S, Syrjänen S. HLA-G and vertical mother-tochild transmission of human papillomavirus infection. Hum. Immunol., 2018, Vol. 79, no. 6, pp. 471-476.Martinetti M., Pacati I., Cuccia M., Badulli C., Pasi A., Salvaneschi L., Minola E., De Silvestri A., Iannone A.M., Maccabruni A. Hierarchy of baby-linked immunogenetic risk factors in the vertical transmission of hepatitis C virus. Int. J. Immunopathol. Pharmacol., 2006, Vol. 19, no. 2, pp. 369-378.Martinetti M., Pacati I., Cuccia M., Badulli C., Pasi A., Salvaneschi L., Minola E., De Silvestri A., Iannone A.M., Maccabruni A. Hierarchy of baby-linked immunogenetic risk factors in the vertical transmission of hepatitis C virus. Int. J. Immunopathol. Pharmacol., 2006, Vol. 19, no. 2, pp. 369-378.Morandi F., Rizzo R., Fainardi E., Rouas-Freiss N., Pistoia V. Recent advances in our understanding of HLA-G biology: lessons from a wide spectrum of human diseases. J. Immunol. Res., 2016, Vol. 2016, 4326495. doi: 10.1155/2016/4326495.Morandi F., Rizzo R., Fainardi E., Rouas-Freiss N., Pistoia V. Recent advances in our understanding of HLA-G biology: lessons from a wide spectrum of human diseases. J. Immunol. Res., 2016, Vol. 2016, 4326495. doi: 10.1155/2016/4326495.Moreau P., Flajollet S., Carosella E.D. Non-classical transcriptional regulation of HLA-G: an update. J. Cell. Mol. Med., 2009, Vol. 13, no. 9B, pp. 2973-2989.Moreau P., Flajollet S., Carosella E.D. Non-classical transcriptional regulation of HLA-G: an update. J. Cell. Mol. Med., 2009, Vol. 13, no. 9B, pp. 2973-2989.Nilsson L.L., Djurisic S., Hviid T.V.F. Controlling the immunological crosstalk during conception and pregnancy: HLA-G in reproduction. Front. Immunol., 2014, Vol. 13, no. 5, 198. doi: 10.3389/fimmu.2014.00198.Nilsson L.L., Djurisic S., Hviid T.V.F. Controlling the immunological crosstalk during conception and pregnancy: HLA-G in reproduction. Front. Immunol., 2014, Vol. 13, no. 5, 198. doi: 10.3389/fimmu.2014.00198.Persson G., Melsted W.N., Nilsson L.L., Hviid T.V.F. HLA class Ib in pregnancy and pregnancy-related disorders. Immunogenetics, 2017, Vol. 69, no. 8-9, pp. 581-595.Persson G., Melsted W.N., Nilsson L.L., Hviid T.V.F. HLA class Ib in pregnancy and pregnancy-related disorders. Immunogenetics, 2017, Vol. 69, no. 8-9, pp. 581-595.Pirri A., Contieri F.C., Benvenutti R., Bicalho M.G. A study of HLA-G polymorphism and linkage disequilibrium in renal transplant patients and their donors. Transpl. Immunol., 2009, Vol. 20, no. 3, pp. 143-149.Pirri A., Contieri F.C., Benvenutti R., Bicalho M.G. A study of HLA-G polymorphism and linkage disequilibrium in renal transplant patients and their donors. Transpl. Immunol., 2009, Vol. 20, no. 3, pp. 143-149.Rebmann V., da Silva Nardi F., Wagner B., Horn P.A. HLA-G as a tolerogenic molecule in transplantation and pregnancy. J. Immunol. Res., 2014, Vol. 2014. 297073. doi: 10.1155/2014/297073.Rebmann V., da Silva Nardi F., Wagner B., Horn P.A. HLA-G as a tolerogenic molecule in transplantation and pregnancy. J. Immunol. Res., 2014, Vol. 2014. 297073. doi: 10.1155/2014/297073.Rebmann V., van der Ven K., Pässler M., Pfeiffer K., Krebs D., Grosse-Wilde H. Association of soluble HLA-G plasma levels with HLA-G alleles. Tissue Antigens, 2001, Vol. 57, pp. 15-21.Rebmann V., van der Ven K., Pässler M., Pfeiffer K., Krebs D., Grosse-Wilde H. Association of soluble HLA-G plasma levels with HLA-G alleles. Tissue Antigens, 2001, Vol. 57, pp. 15-21.Ribeyre C., Carlini F., René C., Jordier F., Picard C., Chiaroni J., Abi-Rached L., Gouret P., Marin G., Molinari N., Chanez P., Paganini J., Gras D., Di Cristofaro J. HLA-G Haplotypes Are Differentially Associated with Asthmatic Features. Front. Immunol., 2018, Vol. 9, 278. doi: 10.3389/fimmu.2018.00278.Ribeyre C., Carlini F., René C., Jordier F., Picard C., Chiaroni J., Abi-Rached L., Gouret P., Marin G., Molinari N., Chanez P., Paganini J., Gras D., Di Cristofaro J. HLA-G Haplotypes Are Differentially Associated with Asthmatic Features. Front. Immunol., 2018, Vol. 9, 278. doi: 10.3389/fimmu.2018.00278.Rizzo R., Gabrielli L., Bortolotti D., Gentili V., Piccirilli G., Chiereghin A., Pavia C., Bolzani S., Guerra B., Simonazzi G., Cervi F., Capretti M.G., Fainardi E., Luca D.D., Landini M.P., Lazzarotto T. Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection. J. Immunol. Res., 2016, Vol. 2016, 3890306. doi: 10.1155/2016/3890306.Rizzo R., Gabrielli L., Bortolotti D., Gentili V., Piccirilli G., Chiereghin A., Pavia C., Bolzani S., Guerra B., Simonazzi G., Cervi F., Capretti M.G., Fainardi E., Luca D.D., Landini M.P., Lazzarotto T. Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection. J. Immunol. Res., 2016, Vol. 2016, 3890306. doi: 10.1155/2016/3890306.Simões R.T., Gonçalves M.A., Castelli E.C., Júnior C.M., Bettini J.S.,Discorde M.L.,Duarte G., Quintana S.M., Simões A.L., Moreau P., Carosella E.D., Soares E.G., Donadi E.A. HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus. Mod. Pathol., 2009, Vol. 22, no. 8, pp. 1075-1082.Simões R.T., Gonçalves M.A., Castelli E.C., Júnior C.M., Bettini J.S.,Discorde M.L.,Duarte G., Quintana S.M., Simões A.L., Moreau P., Carosella E.D., Soares E.G., Donadi E.A. HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus. Mod. Pathol., 2009, Vol. 22, no. 8, pp. 1075-1082.Singh M., Rajak J., Kadam S., Rajadhyaksha S.B. Alloimmunization and role of HLA in pregnancy. Available at: http://dx.doi.org/10.5772/intechopen.84211.Singh M., Rajak J., Kadam S., Rajadhyaksha S.B. Alloimmunization and role of HLA in pregnancy. Available at: http://dx.doi.org/10.5772/intechopen.84211.Stieglitz F., Celik A.A., von Kaisenberg C., Camps M.A., Blasczyk R., Bade-Döding C. The microstructure in the placenta is influenced by the functional diversity of HLA-G allelic variants. Immunogenetics, 2019, Vol. 71, no. 7, pp. 455-463.Stieglitz F., Celik A.A., von Kaisenberg C., Camps M.A., Blasczyk R., Bade-Döding C. The microstructure in the placenta is influenced by the functional diversity of HLA-G allelic variants. Immunogenetics, 2019, Vol. 71, no. 7, pp. 455-463.Tan Z., Shon A.M., Ober C. Evidence of balancing selection at the HLA-G promoter region. Hum. Mol. Genet., 2005, Vol.14, no. 23, pp. 3619-3628.Tan Z., Shon A.M., Ober C. Evidence of balancing selection at the HLA-G promoter region. Hum. Mol. Genet., 2005, Vol.14, no. 23, pp. 3619-3628.Thibodeau V., Lajoie J., Labbe A.C., Zannou M.D., Fowke K.R., Alary M., Poudrier J., Roger M. High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection. PLoS ONE, 2011, Vol. 6, e25185. doi: 10.1371/journal.pone.0025185.Thibodeau V., Lajoie J., Labbe A.C., Zannou M.D., Fowke K.R., Alary M., Poudrier J., Roger M. High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection. PLoS ONE, 2011, Vol. 6, e25185. doi: 10.1371/journal.pone.0025185.Tilburgs T., Evans J.H., Crespo Â.C., Strominger J.L. The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface. Proc. Natl. Acad. Sci. USA, 2015, Vol. 112, no. 43, pp. 13312-13317.Tilburgs T., Evans J.H., Crespo Â.C., Strominger J.L. The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface. Proc. Natl. Acad. Sci. USA, 2015, Vol. 112, no. 43, pp. 13312-13317.Tilburgs T., Strominger J.L. CD8+ effector T cells at the fetal-maternal interface, balancing fetal tolerance and antiviral immunity. Am. J. Reprod. Immunol., 2013, Vol. 69, no. 4, pp. 395-407.Tilburgs T., Strominger J.L. CD8+ effector T cells at the fetal-maternal interface, balancing fetal tolerance and antiviral immunity. Am. J. Reprod. Immunol., 2013, Vol. 69, no. 4, pp. 395-407.Turk W.J., Kimani J., Bielawny T., Wachihi C., Ball T.B., Plummer F.A., Luo M. Associations of human leukocyte antigen-G with resistance and susceptibility to HIV-1 infection in the Pumwani sex worker cohort. AIDS., 2013, Vol. 27, pp. 7-15.Turk W.J., Kimani J., Bielawny T., Wachihi C., Ball T.B., Plummer F.A., Luo M. Associations of human leukocyte antigen-G with resistance and susceptibility to HIV-1 infection in the Pumwani sex worker cohort. AIDS., 2013, Vol. 27, pp. 7-15.Vargas R.G., Sarturi P.R., Mattar S.B., Bompeixe E.P., Silva J.S., Pirri A., Bicalho M.G. Association of HLA-G alleles and 3’ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples. Hum. Immunol., 2011, Vol. 72, no. 6, pp. 479-485.Vargas R.G., Sarturi P.R., Mattar S.B., Bompeixe E.P., Silva J.S., Pirri A., Bicalho M.G. Association of HLA-G alleles and 3’ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples. Hum. Immunol., 2011, Vol. 72, no. 6, pp. 479-485.

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