HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis

Meuleman, Tess; Lashley, Lisa E.E.L.O.; Dekkers, Olaf M.; Lith, J. M. M. van; Claas, Frans H.J.; Bloemenkamp, Kitty W. M.

doi:10.1016/j.humimm.2015.02.004

Cited by 73 publications

(66 citation statements)

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“…Significant associations were observed for phenotypic frequencies of HLA-DRB1*4, HLA-DRB1*13, HLA-DRB1*14 and HLA-DRB1*15 with RPL. However, after correcting for multiple testing none of these were statistically significant [103].…”

Section: Hla-drmentioning

confidence: 85%

“…Mueleman et al did find that HLA-DQ sharing had an OR that trended in favor of association with RPL between HLA-DQB1 and HLA-DQ [103]. Two small studies suggest a linkage between RPL and HLA-DQB1 allele [108,109].…”

Section: Hla-dqmentioning

confidence: 99%

“…Hiby et al also noted that variations in HLA-C2 genotypes independently lead to RPL, especially when this occurs on the paternally derived HLA-C2 [52]. However, a pooled analysis of studies regarding sharing of HLA-C alleles showed no increased risk of RPL [103].…”

Section: Hla-cmentioning

confidence: 99%

“…The meta-analysis by Muelman et al showed an increased risk of RPL in couples with HLA-DR sharing [103]. Another meta-analysis has looked at HLA-DR1 and -DR3 and its links to RPL.…”

Section: Hla-drmentioning

confidence: 99%

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Immunogenetic contributions to recurrent pregnancy loss

Grimstad

Krieg

2016

J Assist Reprod Genet

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While sporadic pregnancy loss is common, occurring in 15 % of pregnancies, recurrent pregnancy loss (RPL) impacts approximately 5 % of couples. Though multiple causes are known (including structural, hormonal, infectious, autoimmune, and thrombophilic causes), after evaluation, roughly half of all cases remain unexplained. The idiopathic RPL cases pose a challenging therapeutic dilemma in addition to incurring much physical and emotional morbidity. Immunogenetic causes have been postulated to contribute to these cases of RPL. Natural Killer cell, T cell expression pattern changes in the endometrium have both been shown in patients with RPL. Human leukocyte antigen (HLA) and cytokine allelic variations have also been studied as etiologies for RPL. Some of the results have been promising, however the studies are small and have not yet put forth outcomes that would change our current diagnosis and management of RPL. Larger database studies are needed with stricter control criteria before reasonable conclusions can be drawn.

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Section: Hla-drmentioning

confidence: 85%

Section: Hla-dqmentioning

confidence: 99%

Section: Hla-cmentioning

confidence: 99%

“…The meta-analysis by Muelman et al showed an increased risk of RPL in couples with HLA-DR sharing [103]. Another meta-analysis has looked at HLA-DR1 and -DR3 and its links to RPL.…”

Section: Hla-drmentioning

confidence: 99%

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Immunogenetic contributions to recurrent pregnancy loss

Grimstad

Krieg

2016

J Assist Reprod Genet

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“…Неоднократно показано, что реализация те-ратогенеза связана с иммунными нарушениями в системе «мать -эмбрион/плод» [13]. Исходя из этого, HLA-G является ключевой молекулой, обеспечивающей иммунные взаимодействия ма-точного микроокружения с аллогенными HLA эмбриона, а нарушения ее экспрессии будут приводить к индукции тератогенеза, связанно-го с фоновыми ксенобиотическими нагрузками.…”

Section: распределение аллелей и генотипов Hla-g 3'utr у женщинunclassified

DISTRIBUTION PATTERNS OF ALLELES AND GENOTYPES FOR HLA-G 3'UTR 14-bp ins/del IN MOTHERS OF CHILDREN WITH CONGENITAL HEART DEFECTS OR REPRODUCTIVE LOSSES AT EARLY GESTATION TERMS

et al. 2017

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Адрес для переписки:Цепокина Анна Викторовна ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний» 652002, Россия, г. Кемерово, Сосновый бульвар, 6. Тел.: 8 (3842) 64-46-50. E-mail: cepoav1991@gmail.com Diseases 650002, Russian Federation, Kemerovo, Sosnoviy blvd, 6. Phone: 7 (3842) 64-46-50. E-mail: cepoav1991@gmail.com иммунология, 2017. Т. 19, № 6. С. 763-770. doi: 10.15789/1563-0625-2017-6-763-770 © Шабалдин А.В. и соавт., 2017 For citation: A.V. Shabaldin, A.V. Tsepokina, S.A. Shmulevich, A.V. Ponasenko, P.M. Kryukov, E.V. Shabaldina /Meditsinskaya Immunologiya, 2017, Vol. 19, no. 6, pp. 763-770. doi: 10.15789/1563-0625-2017-6-763-770 DOI: 10.15789/1563-0625-2017 Резюме. Врожденные пороки сердца являются доминирующей патологией среди всех врожденных пороков плода и новорожденного. Нарушения иммунных взаимодействий в системе «мать -эмбри-он» могут быть следствием тератогенеза. HLA-G является основной молекулой, посредством которой формируется толерантность материнского иммунного микроокружения к полуаллогенному эмбрио-ну. Полиморфный вариант гена HLA-G 3'UTR 14-bp ins/del влияет на устойчивость и экспрессию ма-тричной РНК и тем самым на эффективность блокирования иммунного отторжения полуаллогенно-го эмбриона. Цель исследования была связана с поиском ассоциативных связей между носительством женщинами одного из полиморфных вариантов гена HLA-G 3'UTR 14-bp ins/del с репродуктивными потерями и рождением детей с врожденными пороками сердца. Address for correspondence: Tsepokina Anna V. Research Institute for Complex Issues of CardiovascularОбследовано 103 женщины, имеющие детей с врожденными пороками сердца, 21 женщина с ре-продуктивными потерями до 9 недель беременности и 101 женщина, имеющая двух и более здоровых детей.Выявлено, что маркером ранних репродуктивных потерь у женщин являлся минорный гомозигот-ный генотип HLA-G 3'UTR 14-bp ins/14-bp ins (OR = 5,25; 95%CI = 1,31-21,11) и аллель HLA-G 3'UTR 14-bp ins (OR = 2,34; 95%CI = 1,13-4,84). При носительстве женщиной гетерозиготного вариантного генотипа 14-bp ins/14-bp del HLA-G 3'UTR значимых ассоциаций с рождением детей с ВПС не опре-делено. Abstract. HLA-G is the main molecule through which provides tolerance of maternal immune microenvironment to the semi-allogeneic embryo. Polymorphic variant of 14-bp ins/del in the HLA-G 3'UTR gene affects stability and expression of specific mRNA and, thereby, efficiency of immune rejection blockade of the semi-allogeneic embryo. Immune interactions in the "mother -fetus"system can cause teratogenic effects. Congenital heart defects are the dominant pathology among congenital malformations of the fetus and newborns. The aim of the study was to search possible associations between polymorphic 14-bp ins/del variants of maternal HLA-G 3'UTR gene, and reproductive losses or congenital heart defects in their children. Subjects and Methods. We have examined 103 women who had children with congenital heart defects, 21 women with reproductive losses at up...

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Genetics of Early Miscarriages

Vaiman

2016

Encyclopedia of Life Sciences

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Early miscarriage or early pregnancy loss (EPL) is defined by an embryonic foetal loss occurring before 13 weeks of gestation. In this article, we focus on the genetics of this complex human disease from studies of human patients, sometimes including foetal losses occurring before 20 weeks. Most of the mouse studies on EPL are based on gene invalidation experiments having much wider and pleiotropic effects than a mere defect of implantation or placental development, and therefore they will not be analyzed here. In addition, many good reviews are already available on gene polymorphisms relevant to early miscarriage and are only briefly summarised here. We develop more in‐depth aspects connected to microRNA and copy number variations with EPL, issues that have been much less reviewed in the past. Key Concepts Early pregnancy loss is a complex multifactorial disease, leading to embryo loss in an estimated >70% of the fertilisation events in humans. Besides chromosome anomalies, detected by cytogenetics or CGH arrays (array‐based comparative genomic hybridisation), gene variants are associated with an increased risk of pregnancy loss. These genes may be regulators of immune response including cytokines, modulators of the coagulation cascade, equilibrators of the oxidative stress or, rarely, genes involved in chromosome segregation at meiosis or mitosis. Other genes may be found by genome‐wide association studies. Recent novel studies are developing on the impact of epigenetic regulators (essentially microRNAs) on miscarriages. These can be relevant markers to categorise gene expression deregulation in pregnancy losses.

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HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis

Cited by 73 publications

References 76 publications

Immunogenetic contributions to recurrent pregnancy loss

Immunogenetic contributions to recurrent pregnancy loss

DISTRIBUTION PATTERNS OF ALLELES AND GENOTYPES FOR HLA-G 3'UTR 14-bp ins/del IN MOTHERS OF CHILDREN WITH CONGENITAL HEART DEFECTS OR REPRODUCTIVE LOSSES AT EARLY GESTATION TERMS

Genetics of Early Miscarriages

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