HLA-G in Preeclampsia: a Pilot Study to Propose a Tolerogenic Treatment


  • César Lucio García Faculty of Medicine, Autonomous University of the State of Mexico (UAEMex).
  • Cynthia Ayerim Lucio García Faculty of Medicine, Autonomous University of the State of Mexico (UAEMex).
  • Arely Sarai Alonso Barreto Ciprés Grupo Médico S.C. (CGM)
  • María del Socorro Camarillo Romero Medical Sciences Research Center (CICMED), Autonomous University of the State of Mexico (UAEMex).
  • Cristian Fabian Layton Tovar Coordinación de Hospitales de Alta Especialidad (CHAE), Secretaría de Salud.
  • Deisy Julieth Abril Riaño Universidad El Bosque.
  • Hugo Mendieta Zerón Universidad Autónoma del Estado de México, "Mónica Pretelini Sáenz" Maternal-Perinatal Hospital and Ciprés Grupo Médico S.C. (CGM).




HLA-G, Preeclampsia, Risk Factors, Sexual Intercourse


Background: The serum level of soluble Human Leukocyte Antigen-antigen-D Related (HLA)-(DR) (sHLA-DR) may appear as a useful parameter to monitor maternal immune response during pregnancy. Objective: The aim was to compare HLA-G serum levels in patients with or without preeclampsia.

Methods: Pregnant women seen at the “Mónica Pretelini Sáenz” Maternal-Perinatal Hospital (HMPMPS) were recruited at their first visit. Two groups were conformed: a) women with healthy pregnancies, and b) women with preeclampsia. The patients’ sociodemographic and laboratory data were introduced into the SPSS software program. HLA-G quantification was performed in peripheral blood samples through the Enzyme-linked Immunosorbent Assay (ELISA) method.

Results: The total number of women seen was 16 (mean age, 24 ± 8 years), eight healthy women (mean age, 22 ± 3 years) and eight women with preeclampsia (mean age, 27 ± 7 years). Women with preeclampsia were older, heavier, had higher levels of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), and referred less sexual intercourse per week than healthy pregnant women. There was no difference in HLA-G levels.

Conclusion: The sexual intercourse frequency is a major factor to develop preeclampsia and the serum HLA-G levels measured previous to the child delivery or cesarean are not different between women with or without preeclampsia.


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Author Biography

César Lucio García, Faculty of Medicine, Autonomous University of the State of Mexico (UAEMex).

César Lucio García is a recently graduated MD, beginning his private clinical practice and preparing himself for a Master Degree Program. While student, in August 2017 he was selected for an academic visit in the Department of Robotic and Laparoscopic Surgery at the Moscow Clinical Scientific Center.


Velasco-Murillo V, Navarrete-Hernández E. [Maternal mortality in the IMSS: an analysis from the perspective of mortality and lethality]. Cir Cir 2006 Jan-Feb;74:21–6. spanish

Dekker GA, Sibai BM. The immunology of preeclampsia. Semin Perinatol 1999 Feb;23:24–33.

Saftlas AF, Levine RJ, Klebanoff MA, Martz KL, Ewell MG, Morris CD, et al. Abortion, changed paternity, and risk of preeclampsia in nulliparous women. Am J Epidemiol 2003 Jun;157:1108–14.

Gaber LW, Spargo BH, Lindheimer MD. Renal pathology in pre-eclampsia. Baillieres Clin Obstet Gynaecol 1994 Jun;8:443–68.

Paller MS. Hypertension in pregnancy. J Am Soc Nephrol 1998 Feb;9:314–21.

Mendieta Zerón H1, García Solorio VJ, Nava Díaz PM, Garduño Alanís A, Santillán Benítez JG, Domínguez García V, et al. Hyperleptinemia as a prognostic factor for preeclampsia: a cohort study. Acta Medica (Hradec Kralove) 2012;55:165–171.

Muñoz-Suano A, Hamilton AB, Betz AG. Gimme shelter: the immune system during pregnancy. Immunol Rev 2011 May;241:20–38.

Sado T, Naruse K, Noguchi T, et al. Inflammatory pattern recognition receptors and their ligands: factors contributing to the pathogenesis of preeclampsia. Inflamm Res 2011 Jun;60:509–20.

Rocha N, Neefjes J. MHC class II molecules on the move for successful antigen presentation. EMBO J 2008 Jan; 27:1–5.

Tilburgs T, Scherjon SA, Claas FHJ. Major histocompatibility complex (MHC)-mediated immune regulation of decidual leukocytes at the fetal-maternal interface. J Reprod Immunol 2010 May;85:58–62.

Roussev RG, Coulam CB. HLA-G and its role in implantation (review). J.Assist. Reprod. Genet. 2007 Jul;24:288–295.

Hviid TV. HLA-G in human reproduction: aspects of genetics, function and pregnancy complications. Hum. Reprod. Update 2006 May-Jun;12:209–232.

Saito S, Sakai M, Sasaki Y, Nakashima A, Shiozaki A. Inadequate tolerance induction may induce pre-eclampsia. J Reprod Immunol 2007 Dec;76:30–9.

ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002 Apr;77:67-75.

Saftlas AF, Rubenstein L, Prater K, Harland KK, Field E, Triche E. Cumulative exposure to paternal seminal fluid prior to conception and subsequent risk of preeclampsia. J Reprod Immunol 2014 Mar;101-102:104–110.

Olayemi O, Strobino D, Aimakhu C, Adedapo K, Kehinde A, Odukogbe AT, et al. Influence of duration of sexual cohabitation on the risk of hypertension in nulliparous parturients in Ibadan: A cohort study. Aust N Z J Obstet Gynaecol 2010 Feb;50:40–4.

Kho EM, McCowan LME, North RA, Roberts CT, Chan E, Black MA, et al. Duration of sexual relationship and its effect on preeclampsia and small for gestational age perinatal outcome. J Reprod Immunol 2009 Oct;82:66–73.

Chaiworapongsa T, Romero R, Espinoza J, Bujold E, Mee Kim Y, Gonçalves LF, et al. Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia. Am J Obstet Gynecol 2004 Jun;190:1541–7.

Rizzo R, Andersen AS, Lassen MR, Sørensen HC, 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 Nov;62:320–38.

Yie S, Li L, Li Y, Librach C. HLA-G protein concentrations in maternal serum and placental tissue are decreased in preeclampsia. Am J Obstet Gynecol 2004 Aug;191:525–9.

Steinborn A, Varkonyi T, Scharf A, Bahlmann F, Klee A, Sohn C. Early detection of decreased soluble HLA-G levels in the maternal circulation predicts the occurrence of preeclampsia and intrauterine growth retardation during further course of pregnancy. Am J Reprod Immunol 2007 Apr;57:277–86.

Yie S, Taylor RN, Librach C. Low plasma HLA-G protein concentrations in early gestation indicate the development of preeclampsia later in pregnancy. Am J Obstet Gynecol 2005 Jul;193:204–8.

Hackmon R, Koifman A, Hyodo H, Glickman H, Sheiner E, Geraghty DE. Reduced third-trimester levels of soluble human leukocyte antigen G protein in severe preeclampsia. Am J Obstet Gynecol 2007 Sep;197:255.e1–5.

Vercammen MJ, Verloes A, Van de Velde H, Haentjens P. Accuracy of soluble human leukocyte antigen-G for predicting pregnancy among women undergoing infertility treatment: meta-analysis. Hum Reprod Update 2008 May-Jun; 14:209–218.

Kotze D, Kruger TF, Lombard C, et al. The effect of the biochemical marker soluble human leukocyte antigen G on pregnancy outcome in assisted reproductive technology--a multicenter study. Fertil Steril 2013 Nov;100:1303–9.

Rudstein-Svetlicky N, Loewenthal R, Horejsi V, Gazit E. HLA-G levels in serum and plasma. Tissue Antigens 69 Suppl 2007 Apr;1:140–142.

Wu FX, Wu LJ, Luo XY, Tang Z, Yang MH, Xie CM, et al. Lack of association between HLA-G 14-bp polymorphism and systemic lupus erythematosus in a Han Chinese population. Lupus 2009 Dec;18:1259–66.

Zheng XQ, Li CC, Xu DP, Lin A, Bao WG, Yang GS, Yan WH. Analysis of the plasma soluble human leukocyte antigen-G and interleukin-10 levels in childhood atopic asthma. Hum Immunol 2010 Oct;71:982–7.

Bıyık I. Maternal serum soluble HLA-G in complicated pregnancies. J Matern Fetal Neonatal Med. 2014 Mar;27:381-4.

O'Brien M, McCarthy T, Jenkins D, Paul P, Dausset J, Carosella ED, et al. Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLA-G gene in susceptibility to the disease. Cell Mol Life Sci. 2001 Nov;58:1943-9.

Darmochwal-Kolarz D, Kolarz B, Rolinski J, Leszczynska-Gorzelak B, Oleszczuk J. The concentrations of soluble HLA-G protein are elevated during mid-gestation and decreased in pre-eclampsia. Folia Histochem Cytobiol. 2012 Jul;50:286-91.

Dahl M, Klitkou L, Christiansen OB, Djurisic S, Piosik ZM, Skovbo P, 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 Apr;76:260-71.

Hviid TV, Rizzo R, Melchiorri L, Stignani M, Baricordi OR. Polymorphism in the 5′ Upstream Regulatory and 3′ Untranslated Regions of the HLA-G Gene in Relation to Soluble HLA-G and IL-10 Expression. Hum Immunol. 2006 Jan-Feb;67:53–62.

Rizzo R, Hviid TV, Govoni M, Padovan M, Rubini M, Melchiorri L, et al. HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus. Tissue Antigens 2008 Jun; 71:520–9.

Twito T, Joseph J, Mociornita A, Rao V, Ross H, Delgado DH. The 14-bp deletion in the HLA-G gene indicates a low risk for acute cellular rejection in heart transplant recipients. J Heart Lung Transplant 2011 Jul;30:778–82.

Chen XY, Yan WH, Lin A, Xu HH, Zhang JG, Wang XX. 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 Oct;72:335–41.

Dahl M, Perin TL, Djurisic S, Rasmussen M, Ohlsson J, Buus S, et al. Soluble human leukocyte antigen-G in seminal plasma is associated with HLA-G genotype: possible implications for fertility success. Am J Reprod Immunol 2014 Jul;72:89–105.

Dahl M, Djurisic S, Hviid TVF. The many faces of human leukocyte antigen-G: relevance to the fate of pregnancy. J Immunol Res 2014;2014:591489.

Rao RS, Kumar CG, Prakasham RS, Hobbs PJ. The Taguchi methodology as a statistical tool for biotechnological applications: a critical appraisal. Biotechnol J. 2008 Apr;3:510-23.



How to Cite

Lucio García, C., Lucio García, C. A., Alonso Barreto, A. S., Camarillo Romero, M. del S., Layton Tovar, C. F., Abril Riaño, D. J., & Mendieta Zerón, H. (2018). HLA-G in Preeclampsia: a Pilot Study to Propose a Tolerogenic Treatment. International Journal of Medical Students, 6(2), 56–60. https://doi.org/10.5195/ijms.2018.250