HLA-G基因及其表达在习惯性流产发生中的作用

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总结了国内外现代临床研究的结果，介绍了主要组织相容性复合体（HLA）分子和非经典HLA-G分子在滋养细胞上表达的重要性，特别是在妊娠早期的生理过程中的信息。HLA-G基因在抗原处理和表达方面具有核心功能，并抑制自然杀伤细胞受体，导致母胎界面的免疫反应减少，并为胎儿提供母体免疫耐受。它的表达取决于转录因子、微RNA和环境因素的组合。在此基础上，进行了100多项实验研究，研究HLA-G基因的表达，并证明其对妊娠并发症的发生，如早期习惯性流产的影响，免疫学因素被认为在其中起着关键作用。

作者简介

Margarita O. Bakleycheva

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

Email: bakleicheva@gmail.com
ORCID iD: 0000-0002-0103-8583
Scopus 作者 ID: 57203248029

MD, junior research schientist of Department of obstetrics and perinatology

俄罗斯联邦, 3, Mendeleevskaya Line, Saint Petersburg, 199034

Olesya N. Bespalova

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

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN 代码: 4732-8089

MD, Dr. Sci. (Med.)

俄罗斯联邦, 3, Mendeleevskaya Line, Saint Petersburg, 199034

Tatyana E. Ivashchenko

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

编辑信件的主要联系方式.
Email: tivashchenko2011@mail.ru
ORCID iD: 0000-0002-8549-6505

PhD, Dr. Sci. (Biol.), Professor

俄罗斯联邦, 3, Mendeleevskaya Line, Saint Petersburg, 199034

参考

  1. Djurisic S, Hviid TV. HLA Class Ib molecules and immune cells in pregnancy and preeclampsia. Front Immunol. 2014;5:652. doi: 10.3389/fimmu.2014.00652
  2. Bakleicheva MO, Bespalova ON, Ivashchenko TE. Role of class I HLA (G, E, and C) expression in early reproductive losses. Obstetrics and Gynecology. 2020;(2):30−36. (In Russ.). doi: 10.18565/aig.2020.2.30-36
  3. Carosella ED, Ploussard G, LeMaoult J, Desgrandchamps F. A systematic review of immunotherapy in urologic cancer: Evolving roles for targeting of CTLA-PD-1/PD-L1, and HLA-G. Eur Urol. 2015;68(2):267−279. doi: 10.1016/j.eururo.2015.02.032
  4. Szekeres-Bartho J, Markert UR, Varla-Leftherioti M. Immunology in reproduction. J Reprod Immunol. 2015;108:1. doi: 10.1016/j.jri.2015.03.003
  5. de Wynter EA, Testa NG. Interest of cord blood stem cells. Biomed Pharmacother. 2001;55(4):195−200. doi: 10.1016/s0753-3322(01)00049-x
  6. Serova LD. Immunologicheskij HLA-status u zhenshhin s privychnym nevynashivaniem beremennosti: metodicheskie rekomendacii. Moscow, 1998. (In Russ.)
  7. Steinbrook R. The cord-blood-bank controversies. N Engl J Med. 2004;351(22):2255−2257. doi: 10.1056/NEJMp048283
  8. Ferreira LMR, Meissner TB, Tilburgs T, Strominger JL. HLA-G: At the interface of maternal-fetal tolerance. Trends Immunol. 2017;38:272–286. doi: 10.1016/j.it.2017.01.009
  9. Choudhury SR, Knapp LA. Human reproductive failure II: immunogenetic and interacting factors. Hum Reprod Update. 2001;7(2):135−160. doi: 10.1093/humupd/7.2.135
  10. Lorentzen DF, Iwanaga KK, Meuer KJ, et al. A 25% error rate in serologic typing of HLA-B homozygotes. Tissue Antigens. 1997;50(4):359−365. doi: 10.1111/j.1399-0039.1997.tb02888.x
  11. Komlos L, Zamir R, Joshua H, Halbrecht I. Common HLA antigens in couples with repeated abortions. Clin Immunol Immunopathol. 1977;7(3):330−335. doi: 10.1016/0090-1229(77)90066-6
  12. Christiansen OB, Ring M, Rosgaard A, et al. Association between HLA-DR1 and -DR3 antigens and unexplained repeated miscarriage. Hum Reprod Update. 1999;5(3):249−255. doi: 10.1093/humupd/5.3.249
  13. Dahl M, Klitkou L, Christiansen OB, et al. Human leukocyte antigen (HLA)-G during pregnancy part II: associations between maternal and fetal HLA-G genotypes and soluble HLA-G. Hum Immunol. 2015;76(4):260−271. doi: 10.1016/j.humimm.2015.01.015
  14. Plaks V, Rinkenberger J, Dai J, et al. Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction. Proc Natl Acad Sci USA. 2013;110(27):11109−11114. doi: 10.1073/pnas.1309561110
  15. Zidi I, Rizzo R, Bouaziz A, et al. sHLA-G1 and HLA-G5 levels are decreased in Tunisian women with multiple abortion. Hum Immunol. 2016;77:342–345. doi: 10.1016/j.humimm.2016.01.019
  16. Ikeno M, Suzuki N, Kamiya M, et al. LINE1 family member is negative regulator of HLA-G expression. Nucleic Acids Res. 2012;40(21):10742−10752. doi: 10.1093/nar/gks874
  17. Bespalova O, Bakleicheva M, Ivashchenko T, et al. Expression of HLA-G and KIR2DL4 receptor in chorionic villous in missed abortion. Gynecol Endocrinol. 2020;36(Supp1):43−47. doi: 10.1080/09513590.2020.1816716
  18. Akhter A, Das V, Naik S, et al. Upregulation of HLA-G in JEG-3 cells by dexamethasone and hydrocortisone. Arch Gynecol Obstet. 2012;285(1):7−14. doi: 10.1007/s00404-011-1880-3
  19. Barrientos G, Toro A, Moschansky P, et al. Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways. Placenta. 2015;36(4):419−426. doi: 10.1016/j.placenta.2015.01.006
  20. Gregori S, Amodio G, Quattrone F, Panina-Bordignon P. HLA-G Orchestrates the early interaction of human trophoblasts with the maternal niche. Front Immunol. 2015;6:128. doi: 10.3389/fimmu.2015. 00128
  21. Wang X, Li B, Wang J, et al. Evidence that miR-133a causes recurrent spontaneous abortion by reducing HLA-G expression. Reprod Biomed Online. 2012;25(4):415−424. doi: 10.1016/j.rbmo.2012.06.022
  22. Wu ZS, Wang CQ, Xiang R, et al. Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion. BMC Cancer. 2012;12:51. doi: 10.1186/1471-2407-12-51
  23. Guo W, Fang L, Li B, et al. Decreased human leukocyte antigen-G expression by miR-133a contributes to impairment of proinvasion and proangiogenesis functions of decidual NK cells. Front Immunol. 2017;8:741. doi: 10.3389/fimmu.2017.00741
  24. Rokhafrooz S, Ghadiri A, Ghandil P, et al. Association between HLA-G 14bp gene polymorphism and serum sHLA-G protein concentrations in preeclamptic patients and normal pregnant women. Immunol Invest. 2018;47:558–568. doi: 10.1080/08820139.2018.1467925
  25. Alenichev AS, Nasyhova JuA, Ivashhenko EJe, Baranov VS. Harakteristika geneticheskoj struktury populjacii Severo-Zapadnogo regiona RF po genu HLA-G. Jekologicheskaja genetika. 2014;12(2):74−80. (In Russ.)

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2. 图1 胎儿、胎盘、蜕膜组织及HLA-G表达蛋白分子的功能意义示意图。矩形图显示的是母体和胎儿界面的放大图像，显示滋养细胞群的定位。细胞滋养层细胞是分化的滋养层细胞群的前体；绒毛外滋养细胞（EVT）的表面表达HLA-E、HLA-G，可能还有HLA-F；合胞滋养细胞与绒毛滋养细胞一起，可以表达一种可溶性的HLA-G蛋白分子。圆形插图中的箭头显示HLA-G与细胞表面各种受体的相互作用，即子宫自然杀伤（NK）、CD8+T细胞。ILT—干免疫球蛋白样转录物[1]

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3. 图2 说明HLA-G基因表达减少与习惯性流产中蜕膜自然杀伤功能受损之间关系的假说的示意图。习惯性流产患者的蜕膜NK细胞中KIR2DL4的低表达可能抑制这些细胞的促侵袭和促血管生成细胞因子的分泌。此外，在滋养细胞系HTR-8/SVneo中，miRNA-133a减少了HLA-G基因的表达，可能会影响蜕膜NK细胞与KIR2DL4结合时的分泌能力。细胞因子水平的降低可能影响滋养细胞的侵袭和血管生成。EVT——绒毛外滋养层；VEGF——血管内皮生长因子[23]

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4. 图3 不同人群中HLA-G基因的G*0101-0107等位基因的相似性。使用欧氏距离测量法的沃德法聚类[25]

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