Central European Journal of Biology

, Volume 8, Issue 3, pp 226–239 | Cite as

Role of HLA-G and other immune mechanisms in pregnancy

  • Vladimira DurmanovaEmail author
  • Monika Homolova
  • Juraj Drobny
  • Ivana Shawkatova
  • Milan Buc


Pregnancy loss (abortion) and pre-eclampsia represent the most common disorders in pregnant women. Besides infection, there are anatomical, endocrinological, genetic and immunological factors that can induce pregnancy disorders. Because the exact mechanisms of physiological pregnancy maintenance are still not clearly understood, the search for genes and proteins fulfilling this role is still in progress. One of the immune molecules that plays a beneficial role in pregnancy is the nonclassical HLA-G molecule. The molecule is mainly expressed on trophoblast cells in the foetal placenta and induces the immune tolerance of the foetus via its interaction with inhibitory receptors on maternal NK cells and CD8+ T lymphocytes. In relation to pregnancy disorders, associations between HLA-G polymorphism, HLA-G level and HLA-G function were described. Thus, the HLA-G molecule can be used as a new diagnostic marker and, potentially, for the future therapy of pregnancy disorders.


HLA-G Immunity Human genetics Spontaneous abortion Pre-eclampsia Pregnancy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Sierra S., Stephenson M., Genetics of recurrent pregnancy loss, Semin. Reprod. Med., 2006, 24, 17–24PubMedCrossRefGoogle Scholar
  2. [2]
    Redman Ch.W, Sargent I.L., Latest advances in understanding preeclampsia, Science, 2005, 308, 1592–1594PubMedCrossRefGoogle Scholar
  3. [3]
    Steinberg G., Khankin E.V., Karumanchi S.A., Angiogenic factors and preeclampsia, Thromb Res, 2009, 123, S93–S99PubMedCrossRefGoogle Scholar
  4. [4]
    Roy H., Bhardwaj S., Yla-Herttuala S., Biology of vascular endothelial growth factors, FEBS Lett., 2006, 580, 2879–2887PubMedCrossRefGoogle Scholar
  5. [5]
    Jebbink J., Wolters A., Fernando F., Afink G., van der Post J., Ris-Stalpers C., Molecular genetics of preeclampsia and HELLP syndrome — A review, Bioch. Bioph. Acta, 2012, 1822, 1960–1969CrossRefGoogle Scholar
  6. [6]
    Redman C.W., Sacks G.P., Sargent I.L., Preeclampsia: an excessive maternal inflammatory response to pregnancy, Am. J. Obstet. Gynecol., 1999, 180, 499–506PubMedCrossRefGoogle Scholar
  7. [7]
    Kovats S., Main E.K., Librach C., Stubblebine M., Fisher S.J., DeMars R., A class I antigen, HLA-G, expressed in human trophoblasts, Science, 1990, 248, 220–223PubMedCrossRefGoogle Scholar
  8. [8]
    Wegmann T.G., Lin H., Guilbert L., Mosmann T.R., Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol. Today, 1993, 14, 353–356PubMedCrossRefGoogle Scholar
  9. [9]
    Saito S., Nakashima A., Shima T., Future directions of studies for recurrent miscarriage associated with immune etiologies, J. Reprod. Immunol., 2011, 90, 91–95PubMedCrossRefGoogle Scholar
  10. [10]
    Kwak-Kim J., Yang K.M., Gilman-Sachs A., Recurrent pregnancy loss: a disease of inflammation and coagulation, J. Obstet. Gynaecol. Res., 2009, 35, 609–622PubMedCrossRefGoogle Scholar
  11. [11]
    Bansal A.S., Joining the immunological dots in recurrent miscarriage, Am. J. Reprod. Immunol., 2010, 64, 307–315PubMedGoogle Scholar
  12. [12]
    Clark D.A., Chaouat G., Arck P.C., Mittruecker H.W., Levy G.E., Cytokine-dependent abortion in CBA XDBA/A2 mice is mediated by procoagulant fg12 prothrombinase, J. Immunol., 1998, 160, 545–549PubMedGoogle Scholar
  13. [13]
    Simmelink M.J., Horbach D.A., Derksen R.H., Meijers J.C., Bevers E.M., Willems G.M., et al., Complexes of anti-prothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces, Br. J. Haematol., 2001, 113, 621–629PubMedCrossRefGoogle Scholar
  14. [14]
    Loke Y.W., King A., Burrows T.D., Decidua in human implantation, Hum. Reprod., 1995, 10, 14–21PubMedCrossRefGoogle Scholar
  15. [15]
    King A., Birkby C., Loke Y.W., Early human decidual cells exhibit NK activity against the K562 cell line but not against first trimester trophoblast, Cell Immunol., 1989, 118, 337–344PubMedCrossRefGoogle Scholar
  16. [16]
    Jokhi P.P., King A., Sharkey A.M., Smith S.K., Loke Y.W., Screening for cytokine messenger ribonucleic acids in purified human decidual lymphocyte populations by the reverse-transcriptase polymerase chain reaction, J. Immunol., 1994, 153, 4427–4435PubMedGoogle Scholar
  17. [17]
    King A., Hiby S.E., Gardner L., Joseph S., Bowen J.M., Verma S., et al., Recognition of trophoblast HLA class I molecules by decidual NK cell receptors — a review, Placenta, 2000, 21, S81–85PubMedCrossRefGoogle Scholar
  18. [18]
    Hanna J., Goldman-Wohl D., Hamani Y., Avraham I., Greenfield C., Natanson-Yaron S., et al., Decidual NK cells regulate key developmental processes at the human fetal-maternal interface, Nat. Med., 2006, 12, 1065–1074PubMedCrossRefGoogle Scholar
  19. [19]
    Hong Y., Wang X., Lu P., Song Y., Lin Q., Killer immunoglobulin-like receptor repertoire on uterine natural killer cell subsets in women with recurrent spontaneous abortions, Eur. J. Obstet. Gynecol. Reprod. Biol., 2008, 140, 218–223PubMedCrossRefGoogle Scholar
  20. [20]
    Wilczyński J.R., Tchórzewski H., Banasik M., Głowacka E., Wieczorek A., Lewkowicz P., et al., Lymphocyte subset distribution and cytokine secretion in third trimester decidua in normal pregnancy and preeclampsia, Eur. J. Obstet. Gynecol. Reprod. Biol., 2003, 109, 8–15PubMedCrossRefGoogle Scholar
  21. [21]
    Aschkenazi S., Straszewski S., Verwer K.M., Foellmer H., Rutherford T., Mor G., Differential regulation and function of the Fas/Fas ligand system in human trophoblast cells, Biol Reprod., 2002, 66, 1853–1861PubMedCrossRefGoogle Scholar
  22. [22]
    Rezaei A., Dabbagh A., T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion, Med. Sci. Monit., 2002, 8, CR607–610PubMedGoogle Scholar
  23. [23]
    Kwak-Kim J.Y., Chung-Bang H.S., Ng S.C., Ntrivalas E.I., Mangubat C.P., Beaman K.D., et al., Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF, Hum. Reprod., 2003, 18, 767–773PubMedCrossRefGoogle Scholar
  24. [24]
    Sharma A., Satyam A., Sharma J.B. Leptin, IL-10 and inflammatory markers (TNF-alpha, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women, Am. J. Reprod. Immunol., 2007, 58, 21–30PubMedCrossRefGoogle Scholar
  25. [25]
    Somerset D.A., Zheng Y., Kilby M.D., Sansom D.M., Drayson M.T., Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset, Immunology, 2004, 112, 38–43PubMedCrossRefGoogle Scholar
  26. [26]
    Schumacher A., Brachwitz N., Sohr S., Engeland K., Langwisch S., Dolaptchieva M., et al., Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy, J. Immunol., 2009, 182, 5488–5497PubMedCrossRefGoogle Scholar
  27. [27]
    Piccirillo C.A., Shevach E.M., Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance, Semin. Immunol., 2004, 16, 81–88PubMedCrossRefGoogle Scholar
  28. [28]
    Fallarino F., Grohmann U., Hwang K.W., Orabona C., Vacca C., Bianchi R., et al., Modulation of tryptophan catabolism by regulatory T cells, Nat. Immunol., 2003, 4, 1206–1212PubMedCrossRefGoogle Scholar
  29. [29]
    López A.S., Alegre E., LeMaoult J., Carosella E., González A., Regulatory role of tryptophan degradation pathway in HLA-G expression by human monocyte-derived dendritic cells, Mol. Immunol., 2006, 43, 2151–2160PubMedCrossRefGoogle Scholar
  30. [30]
    Jin L.P., Chen Q.Y., Zhang T., Guo P.F., Li D.J., The CD4+CD25 bright regulatory T cells and CTLA-4 expression in peripheral and decidual lymphocytes are down-regulated in human miscarriage, Clin. Immunol., 2009, 133, 402–410PubMedCrossRefGoogle Scholar
  31. [31]
    Saito S., Shiozaki A., Sasaki Y., Nakashima A., Shima T., Ito M., Regulatory T cells and regulatory natural killer (NK) cells play important roles in fetomaternal tolerance, Semin. Immunopathol., 2007, 29, 115–122PubMedCrossRefGoogle Scholar
  32. [32]
    Harrington L.E., Mangan P.R., Weaver C.T., Expanding the effector CD4 T-cell repertoire: the Th17 lineage, Curr. Opin. Immunol., 2006, 18, 349–356PubMedCrossRefGoogle Scholar
  33. [33]
    Pongcharoen S., Somran J., Sritippayawan S., Niumsup P., Chanchan P., Butkhamchot P., et al., Interleukin-17 expression in the human placenta, Placenta, 2007, 28, 59–63PubMedCrossRefGoogle Scholar
  34. [34]
    Arruvito L., Billordo A., Capucchio M., Prada M.E., Fainboim L., IL-6 trans-signaling and the frequency of CD4+FOXP3+ cells in women with reproductive failure, J. Reprod. Immunol., 2009, 82, 158–165PubMedCrossRefGoogle Scholar
  35. [35]
    Santner-Nanan B., Peek M.J., Khanam R., Richarts L., Zhu E., Fazekas de St Groth B., et al., Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia, J. Immunol., 2009, 183, 7023–7030PubMedCrossRefGoogle Scholar
  36. [36]
    Molina H., Complement regulation during pregnancy, Immunol. Res., 2005, 32, 187–192PubMedCrossRefGoogle Scholar
  37. [37]
    Sugiura-Ogasawara M., Nozawa K., Nakanishi T., Hattori Y., Ozaki Y., Complement as a predictor of further miscarriage in couples with recurrent miscarriages, Hum. Reprod., 2006, 21, 2711–2714PubMedCrossRefGoogle Scholar
  38. [38]
    Rouas-Freiss N., Gonçalves R.M., Menier C., Dausset J., Carosella E.D., Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis, Proc. Natl. Acad. Sci. U S A, 1997, 94, 11520–11525PubMedCrossRefGoogle Scholar
  39. [39]
    Valés-Gómez M., Reyburn H.T., Mandelboim M., Strominger J.L., Kinetics of interaction of HLA-C ligands with natural killer cell inhibitory receptors, Immunity, 1998, 9, 337–344PubMedCrossRefGoogle Scholar
  40. [40]
    Braud V.M., Allan D.S., O’Callaghan C.A., Söderström K., D’Andrea A., Ogg G.S., et al., HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C, Nature, 1998, 391, 795–799PubMedCrossRefGoogle Scholar
  41. [41]
    Ober C., Aldrich C.L., Chervoneva I., Billstrand C., Rahimov F., Gray H.L., et al., Variation in the HLA-G promoter region influences miscarriage rates, Am. J. Hum. Genet., 2003, 72, 1425–1435PubMedCrossRefGoogle Scholar
  42. [42]
    Yie S.M., Li L.H., Xiao R., Librach C.L., A single base-pair mutation in the 3′-untranslated region of HLA-G mRNA is associated with pre-eclampsia, Mol. Hum. Reprod., 2008, 14, 649–653PubMedCrossRefGoogle Scholar
  43. [43]
    Geraghty D.E., Koller B.H., Orr H.T., A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment, Proc. Natl. Acad. Sci. U S A, 1987, 84, 9145–9149PubMedCrossRefGoogle Scholar
  44. [44]
    Ishitani A., Geraghty D.E., Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens, Proc. Natl. Acad. Sci. U S A, 1992, 89, 3947–3951PubMedCrossRefGoogle Scholar
  45. [45]
    Crisa L., McMaster M.T., Ishii J.K., Fisher S.J., Salomon D.R., Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts, J. Exp. Med., 1997, 186, 289–298PubMedCrossRefGoogle Scholar
  46. [46]
    Onno M., Guillaudeux T., Amiot L., Renard I., Drenou B., Hirel B., et al., The HLA-G gene is expressed at a low mRNA level in different human cells and tissues, Hum. Immunol., 1994, 41, 79–86PubMedCrossRefGoogle Scholar
  47. [47]
    Yang Y., Chu W., Geraghty D.E., Hunt J.S., Expression of HLA-G in human mononuclear phagocytes and selective induction by IFN-gamma, J. Immunol., 1996, 156, 4224–4231PubMedGoogle Scholar
  48. [48]
    Lila N., Carpentier A., Amrein C., Khalil-Daher I., Dausset J., Carosella E.D., Implication of HLA-G molecule in heart-graft acceptance, Lancet, 2000, 355, 2138PubMedCrossRefGoogle Scholar
  49. [49]
    Lila N., Amrein C., Guillemain R., Chevalier P., Latremouille C., Fabiani J.N., et al., Human leukocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection, Circulation, 2002, 105, 1949–1954PubMedCrossRefGoogle Scholar
  50. [50]
    Qiu J., Terasaki P.I., Miller J., Mizutani K., Cai J., Carosella ED., Soluble HLA-G expression and renal graft acceptance, Am. J. Transpl., 2006, 6, 2152–2156CrossRefGoogle Scholar
  51. [51]
    Rebmann V., Regel J., Stolke D., Grosse-Wilde H., Secretion of sHLA-G molecules in malignancies, Semin. Cancer. Biol., 2003, 13, 371–377PubMedCrossRefGoogle Scholar
  52. [52]
    Ye S.R., Yang H., Li K., Dong D.D., Lin X.M., Yie S.M., Human leukocyte antigen G expression: as a significant prognostic indicator for patients with colorectal cancer, Mod. Pathol., 2007, 20, 375–383PubMedCrossRefGoogle Scholar
  53. [53]
    Yan W.H., Lin A., Chen B.G., Chen S.Y., Induction of both membrane-bound and soluble HLA-G expression in active human cytomegalovirus infection, J. Infect. Dis., 2009, 200, 820–826PubMedCrossRefGoogle Scholar
  54. [54]
    Rosado S., Perez-Chacon G., Mellor-Pita S., Sanchez-Vegazo I., Bellas-Menendez C., Citores M.J., et al., Expression of human leukocyte antigen-G in systemic lupus erythematosus, Hum. Immunol., 2008, 69, 9–15PubMedCrossRefGoogle Scholar
  55. [55]
    Wastowski I.J., Sampaio-Barros P.D., Amstalden E.M., Palomoni G.M., Marques-Neto J.F., Crispim J.C., et al, HLA-G expression in the skin of patients with systemic sclerosis, J. Rheumatol., 2009, 36, 1230–1234PubMedCrossRefGoogle Scholar
  56. [56]
    Riteau B., Moreau P., Menier C., Khalil-Daher I., Khosrotehrani K., Bras-Goncalves R., et al., Characterization of HLA-G1, -G2, -G3, and -G4 isoforms transfected in a human melanoma cell line, Transplant. Proc., 2001, 33, 2360–2364PubMedCrossRefGoogle Scholar
  57. [57]
    LeMaoult J., Zafaranloo K., Le Danff C., Carosella E.D., HLA-G up-regulates ILT2, ILT3, ILT4 and KIR2DL4 in antigen presenting cells, NK cells and T cells, FASEB J., 2005, 19, 662–664PubMedGoogle Scholar
  58. [58]
    Contini P., Ghio M., Poggi A., Filaci G., Indiveri F., Ferrone S., et al., Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation, Eur. J. Immunol., 2003, 33, 125–134PubMedCrossRefGoogle Scholar
  59. [59]
    Lee N., Malacko A.R., Ishitani A., Chen M.C., Bajorath J., Marquardt H., et al., The membranebound and soluble forms of HLA-G bind identical sets of endogenous peptides but differ with respect to TAP association, Immunity, 1995, 3, 591–600PubMedCrossRefGoogle Scholar
  60. [60]
    Diehl M., Münz C., Keilholz W., Stevanović S., Holmes N., Loke Y.W., et al., Nonclassical HLA-G molecules are classical peptide presenters, Curr. Biol., 1996, 6, 305–314PubMedCrossRefGoogle Scholar
  61. [61]
    Suárez M.B., Morales P., Castro M.J., Fernández V., Varela P., Alvarez M., et al., A new HLA-G allele (HLA-G*0105N) and its distribution in the Spanish population, Immunogenetics, 1997, 45, 464–465PubMedCrossRefGoogle Scholar
  62. [62]
    Le Discorde M., Le Danff C., Moreau P., Rouas-Freiss N., Carosella E.D., HLA-G*0105N null allele encodes functional HLA-G isoforms, Biol. Reprod., 2005, 73, 280–288PubMedCrossRefGoogle Scholar
  63. [63]
    Larsen M.H., Hviid T.V.F., Human leukocyte antigen-G polymorphism in relation to expression, function and disease, Hum. Immunol., 2009, 70, 1026–1034PubMedCrossRefGoogle Scholar
  64. [64]
    van der Ven K., Skrablin S., Engels G., Krebs D., HLA-G polymorphisms and allele frequencies in Caucasians, Hum. Immunol., 1998, 59, 302–312PubMedCrossRefGoogle Scholar
  65. [65]
    Yamashita T., Fujii T., Tokunaga K., Tadokoro K., Hamai Y., Miki A., et al., Analysis of human leukocyte antigen-G polymorphism including intron 4 in Japanese couples with habitual abortion, Am. J. Reprod. Immunol., 1999, 41, 159–163PubMedCrossRefGoogle Scholar
  66. [66]
    Ishitani A., Kishida M., Sageshima N., Yashiki S., Sonoda S., Hayami M., Smith A.G., Hatake K., Re-examination of HLA-G polymorphism in African Americans, Immunogenetics, 1999, 49, 808–811PubMedCrossRefGoogle Scholar
  67. [67]
    Tan C.Y., Ho J.F., Chong Y.S., Loganath A., Chan Y.H., Ravichandran J., et al., Paternal contribution of HLA-G*0106 significantly increases risk for preeclampsia in multigravid pregnancies, Mol. Hum. Reprod., 2008, 14, 317–324PubMedCrossRefGoogle Scholar
  68. [68]
    Hviid T.V., HLA-G in human reproduction: aspects of genetics, function and pregnancy complications, Hum. Reprod. Update, 2006, 12, 209–232PubMedCrossRefGoogle Scholar
  69. [69]
    Gobin S.J., Keijsers V., van Zutphen M., van den Elsen P.J., The role of enhancer A in the locus-specific transactivation of classical and nonclassical HLA class I genes by nuclear factor kappa B, J. Immunol., 1998, 161, 2276–2283PubMedGoogle Scholar
  70. [70]
    Gobin S.J., van Zutphen M., Woltman A.M., van den Elsen P.J., Transactivation of classical and nonclassical HLA class I genes through the IFNstimulated response element, J. Immunol., 1999, 163, 1428–1434PubMedGoogle Scholar
  71. [71]
    Nicolae D., Cox N.J., Lester L.A., Schneider D., Tan Z., Billstrand C., et al., Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21, Am. J. Hum. Genet., 2005, 76, 349–357PubMedCrossRefGoogle Scholar
  72. [72]
    Rousseau P., Le Discorde M., Mouillot G., Marcou C., Carosella E.D., Moreau P., The 14 bp deletion-insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability, Hum. Immunol., 2003, 64, 1005–1010PubMedCrossRefGoogle Scholar
  73. [73]
    Hviid T.V., Hylenius S., Rørbye C., Nielsen L.G., HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels, Immunogenetics, 2003, 55, 63–79PubMedGoogle Scholar
  74. [74]
    Chen X.Y., Yan W.H., Lin A., Xu H.H., Zhang J.G., Wang X.X., The 14 bp deletion polymorphisms in HLA-G gene play an important role in the expression of soluble HLA-G in plasma, Tissue Antigens, 2008, 72, 335–341PubMedCrossRefGoogle Scholar
  75. [75]
    Tan Z., Randall G., Fan J., Camoretti-Mercado B., Brockman-Schneider R., Pan L., et al., Allelespecific targeting of microRNAs to HLA-G and risk of asthma, Am. J. Hum. Genet., 2007, 81, 829–834PubMedCrossRefGoogle Scholar
  76. [76]
    Ellis S.A., Palmer M.S., McMichael A.J., Human trophoblast and the choriocarcinoma cell line BeWo express a truncated HLA Class I molecule, J. Immunol., 1990, 144, 731–735PubMedGoogle Scholar
  77. [77]
    Noci I., Fuzzi B., Rizzo R., Melchiorri L., Criscuoli L., Dabizzi S., et al., Embryonic soluble HLA-G as a marker of developmental potential in embryos, Hum. Reprod., 2005, 20, 138–146PubMedCrossRefGoogle Scholar
  78. [78]
    Rizzo R., Fuzzi B., Stignani M., Criscuoli L., Melchiorri L., Dabizzi S., et al., Soluble HLA-G molecules in follicular fluid: a tool for oocyte selection in IVF? J. Reprod. Immunol., 2007, 74, 133–142PubMedCrossRefGoogle Scholar
  79. [79]
    Pfeiffer K.A., Fimmers R., Engels G., van der Ven H., van der Ven K., The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion, Mol. Hum. Reprod., 2001, 7, 373–378PubMedCrossRefGoogle Scholar
  80. [80]
    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, 57, 15–21PubMedCrossRefGoogle Scholar
  81. [81]
    Yie S.M., Taylor R.N., Librach C., Low plasma HLA-G protein concentrations in early gestation indicates the development of preeclampsia later in pregnancy, Am. J. Obstet. Gynecol., 2005, 193, 204–208PubMedCrossRefGoogle Scholar
  82. [82]
    Rizzo R., Andersen A.S., Lassen M.R., Sorensen H.C., Bergholt T., Larsen MH, et al., Soluble human leukocyte antigen-G isoforms in maternal plasma in early and late pregnancy, Am. J. Reprod. Immunol., 2009, 62, 320–338PubMedCrossRefGoogle Scholar
  83. [83]
    Zhu X., Han T., Yin G., Wang X., Yao Y., Expression of human leukocyte antigen-G during normal placentation and in preeclamptic pregnancies, Hypertens. Pregnancy, 2012, 31, 252–260PubMedCrossRefGoogle Scholar
  84. [84]
    Steinborn A., Rebmann V., Scharf A., Sohn C., Grosse-Wilde H., Placental abruption is associated with decreased maternal plasma levels of soluble HLA-G, J. Clin. Immunol., 2003, 23, 307–314PubMedCrossRefGoogle Scholar
  85. [85]
    Karhukorpi J., Laitinen T., Tjilikainen A.S., HLA-G polymorphism in Finnish couples with recurrent spontaneous miscarriage, Br. J. Obstet. Gynaecol., 1997, 104, 1212–1214PubMedCrossRefGoogle Scholar
  86. [86]
    Sipak-Szmigiel O., Cybulski C., Lubiński J., Ronin-Walknowska E., HLA-G polymorphism in a Polish population and reproductive failure, Tissue Antigens, 2008, 71, 67–71PubMedGoogle Scholar
  87. [87]
    Yan W.H., Fan L.A., Yang J.Q., Xu L.D., Ge Y., Yao F.J., HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortion, Int. J. Immunogenetics, 2006, 33, 55–58CrossRefGoogle Scholar
  88. [88]
    Aruna M., Sudheer P.S., Andal S., Tarakeswari S., Reddy A.G., Thangaraj K., Singh L., Reddy B.M., HLA-G polymorphism patterns show lack of detectable association with recurrent spontaneous abortion, Tissue Antigens, 2010, 76, 216–222PubMedCrossRefGoogle Scholar
  89. [89]
    Aruna M., Sirisha P.V., Andal Bhaskar S., Tarakeswari S., Thangaraj K., Reddy B.M., Role of 14-bp insertion/deletion polymorphism in HLA-G among Indian women with recurrent spontaneous abortions, Tissue Antigens, 2011, 77, 131–135PubMedCrossRefGoogle Scholar
  90. [90]
    Bermingham J., Jenkins D., McCarthy T., O’Brien M., Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia, Biochem. Soc. Trans., 2000, 28, 215–219PubMedGoogle Scholar
  91. [91]
    Vianna P., Dalmáz C.A., Veit T.D., Tedoldi C., Roisenberg I., Chies J.A., Immunogenetics of pregnancy: role of a 14-bp deletion in the maternal HLA-G gene in primiparous pre-eclamptic Brazilian women, Hum. Immunol., 2007, 68, 668–674PubMedCrossRefGoogle Scholar
  92. [92]
    Iversen A.C., Nguyen O.T., Tømmerdal L.F., Eide I.P., Landsem V.M., Acar N., et al., The HLA-G 14bp gene polymorphism and decidual HLA-G 14bp gene expression in pre-eclamptic and normal pregnancies, J. Reprod. Immunol., 2008, 78, 158–165PubMedCrossRefGoogle Scholar
  93. [93]
    Aldrich C.L., Stephenson M.D., Karrison T., Odem R.R., Branch D.W., Scott J.R., et al., HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage, Mol. Hum. Reprod., 2001, 7, 1167–1172PubMedCrossRefGoogle Scholar
  94. [94]
    Moreau P., Contu L., Alba F., Lai S., Simoes R., Orrù S., et al., HLA-G gene polymorphism in human placentas: possible association of G*0106 allele with preeclampsia and miscarriage, Biol. Reprod., 2008, 79, 459–467PubMedCrossRefGoogle Scholar
  95. [95]
    Tan C.Y., Ho J.F., Chong Y.S., Loganath A., Chan Y.H., Ravichandran J., et al., Paternal contribution of HLA-G*0106 significantly increases risk for preeclampsia in multigravid pregnancies, Mol. Hum. Reprod., 2008, 14, 317–324PubMedCrossRefGoogle Scholar
  96. [96]
    Hviid T.V., Hylenius S., Hoegh A.M., Kruse C., Christiansen O.B., HLA-G polymorphisms in couples with recurrent spontaneous abortions, Tissue Antigens, 2002, 60, 122–132PubMedCrossRefGoogle Scholar
  97. [97]
    Berger D.S., Hogge W.A., Barmada M.M., Ferrell R.E., Comprehensive analysis of HLA-G: implications for recurrent spontaneous abortion, Reprod. Sci., 2010, 17, 331–338PubMedCrossRefGoogle Scholar
  98. [98]
    Zhu Y., Huo Z., Lai J., Li S., Jiao H., Dang J., et al., Case-control study of a HLA-G 14-bp insertion-deletion polymorphism in women with recurrent miscarriages, Scand. J. Immunol., 2010, 71, 52–54PubMedCrossRefGoogle Scholar
  99. [99]
    Hylenius S., Andersen A.M., Melbye M., Hviid T.V., Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads, Mol. Hum. Reprod., 2004, 10, 237–246PubMedCrossRefGoogle Scholar
  100. [100]
    Xue S., Yang J., Yao F., Xu L., Fan L., Recurrent spontaneous abortions patients have more -14 bp/+14 bp heterozygotes in the 3′UT region of the HLA-G gene in a Chinese Han population, Tissue Antigens, 2007, 69, 153–155PubMedCrossRefGoogle Scholar
  101. [101]
    Shankarkumar U., Shankarkumar A., Chedda Z., Ghosh K., Role of 14-bp deletion/insertion polymorphism in exon 8 of the HLA-G gene in recurrent spontaneous abortion patients, J. Hum. Reprod. Sci., 2011, 4, 143–146PubMedCrossRefGoogle Scholar
  102. [102]
    Vargas R.G., Sarturi P.R., Mattar S.B., Bompeixe E.P., Silva Jdos S., Pirri A., et al., Association of HLA-G alleles and 3’ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples, Hum. Immunol., 2011, 72, 479–485PubMedCrossRefGoogle Scholar
  103. [103]
    Larsen M.H., Hylenius S., Andersen A.M., Hviid T.V.F., The 3’-untranslated region of the HLA-G gene in relation to pre-eclampsia: revisited, Tissue Antigens, 2010, 75, 253–261PubMedCrossRefGoogle Scholar
  104. [104]
    Jassem R.M., Shani W.S., Loisel D.A., Sharief M., Billstrand C., Ober C., HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent pregnancy loss from Basrah province in Iraq, Hum. Immunol., 2012, 73, 811–817PubMedCrossRefGoogle Scholar
  105. [105]
    Zhang Z., Li Y., Zhang L.L., Jia L.T., Yang X.Q., Association of 14 bp insertion/deletion polymorphism of the HLA-G gene in father with severe preeclampsia in Chinese, Tissue Antigens, 2012, 80, 158–164PubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Wien 2012

Authors and Affiliations

  • Vladimira Durmanova
    • 1
    Email author
  • Monika Homolova
    • 1
  • Juraj Drobny
    • 2
  • Ivana Shawkatova
    • 1
  • Milan Buc
    • 1
  1. 1.Institute of Immunology, School of MedicineComenius UniversityBratislavaSlovakia
  2. 2.1st Department of Obstetrics and Gynaecology, University Hospital, School of MedicineComenius UniversityBratislavaSlovakia

Personalised recommendations