Cytomegalovirus specific cell-mediated immunity status in women with preeclampsia: A case-control study


1 Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Obstetrics and Gynecology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Epidemiology and Biostatistics, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Preeclampsia, a pregnancy-specific complication, has been associated with cytomegalovirus (CMV) infection in observational studies. CMV-specific T cell response plays a major role in viremia clearance. We explored whether CMV-specific cell-mediated immunity (CMI) status is associated with preeclampsia in pregnant women.
Materials and Methods: CMV-specific CMI was assessed using CMV-QuantiFERON (QF-CMV) assay in plasma serum of 35 women with preeclampsia as well as 35 normal pregnant controls, retrospectively. Participants were matched for gestational age in a 1:1 ratio. The proportion of reactive results, the mean value of interferon-gamma (IFN-γ) level produced in mitogen and antigen tubes were compared between the cases and controls through Chi-square and Wilcoxon rank-sum tests, respectively. The odds ratio and confidence interval were calculated as well.
Results: No significant differences observed between demographic characteristics of the case and control groups. The QF-CMV assay turned reactive (QF-CMV [ + ]) Women with preeclampsia had lower mean IFN-γ levels in antigen tube compared with normal pregnant controls. There were no statistically significant differences in the value of mitogen tube between case and controls women with suppressed CMV-CMI were 6.3 times more likely to have preeclampsia. This result even strengthened after adjustment for age, gestational age, and gravidity.
Conclusions: Our findings support an association between suppressed CMV-specific CMI and preeclampsia.


Kharaghani R, Cheraghi Z, Okhovat Esfahani B, Mohammadian Z, Nooreldinc RS. Prevalence of preeclampsia and eclampsia in Iran. Arch Iran Med 2016;19:64-71.  Back to cited text no. 1
Subki AH, Algethami MR, Baabdullah WM, Alnefaie MN, Alzanbagi MA, Alsolami RM, et al. Prevalence, risk factors, and fetal and maternal outcomes of hypertensive disorders of pregnancy: A retrospective study in Western Saudi Arabia. Oman Med J 2018;33:409-415.  Back to cited text no. 2
Xie F, von Dadelszen P, Nadeau J. CMV infection, TLR-2 and -4 expression, and cytokine profiles in early-onset preeclampsia with HELLP syndrome. Am J Reprod Immunol 2014;71:379-86.  Back to cited text no. 3
Molvarec A, Shiozaki A, Ito M, Toldi G, Stenczer B, Szarka A, et al. Increased prevalence of peripheral blood granulysin-producing cytotoxic T lymphocytes in preeclampsia. J Reprod Immunol 2011;91:56-63.  Back to cited text no. 4
Leghmar K, Cenac N, Rolland M, Martin H, Rauwel B, Bertrand-Michel J, et al. Cytomegalovirus infection triggers the secretion of the PPARγ agonists 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) in human cytotrophoblasts and placental cultures. PLoS One 2015;10:e0132627.  Back to cited text no. 5
Tabata T, Petitt M, Fang-Hoover J, Rivera J, Nozawa N, Shiboski S, et al. Cytomegalovirus impairs cytotrophoblast-induced lymphangiogenesis and vascular remodeling in an in vivo human placentation model. Am J Pathol 2012;181:1540-59.  Back to cited text no. 6
Warner JA, Zwezdaryk KJ, Day B, Sullivan DE, Pridjian G, Morris CA. Human cytomegalovirus infection inhibits CXCL12- mediated migration and invasion of human extravillous cytotrophoblasts. Virol J 2012;9:255.  Back to cited text no. 7
Rana S, Venkatesha S, DePaepe M, Chien EK, Paglia M, Karumanchi SA. Cytomegalovirus-induced mirror syndrome associated with elevated levels of circulating antiangiogenic factors. Obstet Gynecol 2007;109:549-52.  Back to cited text no. 8
Alvarado-Esquivel C, Sandoval-Carrillo AA, Vazquez-Alaniz F, Salas-Pacheco JM, Hernández-Tinoco J, Sánchez-Anguiano LF, et al. Lack of association between cytomegalovirus infection and hypertensive disorders in pregnancy: A case-control study in Durango, Mexico. Eur J Microbiol Immunol (Bp) 2017;7:229-33.  Back to cited text no. 9
von Dadelszen P, Magee LA, Krajden M, Alasaly K, Popovska V, Devarakonda RM, et al. Levels of antibodies against cytomegalovirus and Chlamydophila pneumoniae are increased in early onset pre-eclampsia. BJOG 2003;110:725-30.  Back to cited text no. 10
Strand KM, Odland ML, Iversen AC, Nordbø SA, Vik T, Austgulen R. Cytomegalovirus antibody status at 17-18 weeks of gestation and pre-eclampsia: A case-control study of pregnant women in Norway. BJOG 2012;119:1316-23.  Back to cited text no. 11
Shaiegan M, Rasouli M, Zadsar M, Zolfaghari S. Meta-analysis of cytomegalovirus seroprevalence in volunteer blood donors and healthy subjects in Iran from 1992 to 2013. Iran J Basic Med Sci 2015;18:627-34.  Back to cited text no. 12
Kumar D, Chernenko S, Moussa G, Cobos I, Manuel O, Preiksaitis J, et al. Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients. Am J Transplant 2009;9:1214-22.  Back to cited text no. 13
Lochmanova A, Lochman I, Tomaskova H, Marsalkova P, Raszka J, Mrazek J, et al. Quantiferon-CMV test in prediction of cytomegalovirus infection after kidney transplantation. Transplant Proc 2010;42:3574-7.  Back to cited text no. 14
Walker S, Fazou C, Crough T, Holdsworth R, Kiely P, Veale M, et al. Ex vivo monitoring of human cytomegalovirus-specific CD8+ T-cell responses using QuantiFERON-CMV. Transpl Infect Dis 2007;9:165-70.  Back to cited text no. 15
Westall GP, Mifsud NA, Kotsimbos T. Linking CMV serostatus to episodes of CMV reactivation following lung transplantation by measuring CMV-specific CD8+ T-cell immunity. Am J Transplant 2008;8:1749-54.  Back to cited text no. 16
Kumar D, Mian M, Singer L, Humar A. An interventional study using cell-mediated immunity to personalize therapy for cytomegalovirus infection after transplantation. Am J Transplant 2017;17:2468-73.  Back to cited text no. 17
Abate D, Saldan A, Mengoli C, Fiscon M, Silvestre C, Fallico L, et al. Comparison of cytomegalovirus (CMV) enzyme-linked immunosorbent spot and CMV quantiferon gamma interferon-releasing assays in assessing risk of CMV infection in kidney transplant recipients. J Clin Microbiol 2013;51:2501-7.  Back to cited text no. 18
Lisboa LF, Kumar D, Wilson LE, Humar A. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation 2012;93:195-200.  Back to cited text no. 19
Deborska-Materkowska D, Perkowska-Ptasinska A, Sadowska A, Gozdowska J, Ciszek M, Serwanska-Swietek M, et al. Diagnostic utility of monitoring cytomegalovirus-specific immunity by QuantiFERON-cytomegalovirus assay in kidney transplant recipients. BMC Infect Dis 2018;18:179.  Back to cited text no. 20
Thompson G, Boan P, Baumwol J, Chakera A, MacQuillan G, Swaminathan S, et al. Analysis of the QuantiFERON-CMV assay, CMV viraemia and antiviral treatment following solid organ transplantation in Western Australia. Pathology 2018;50:554-61.  Back to cited text no. 21
Freer G, Quaranta P, Pistello M. Evaluation of T cell immunity against human cytomegalovirus: Impact on patient management and risk assessment of vertical transmission. J Immunol Res 2016;2016:1-8.  Back to cited text no. 22
Hui J, Qu YY, Tang N, Liu YM, Zhong H, Wang LM, et al. Association of cytomegalovirus infection with hypertension risk: A meta-analysis. Wien Klin Wochenschr 2016;128:586-91.  Back to cited text no. 23
Radcliffe JJ, Hart CA, Francis WJ, Johnson PM. Immunity to cytomegalovirus in women with unexplained recurrent spontaneous abortion. Am J Reprod Immunol Microbiol 1986;12:103-5.  Back to cited text no. 24
Xie F, Hu Y, Magee LA, Money DM, Patrick DM, Krajden M, et al. An association between cytomegalovirus infection and pre-eclampsia: A case-control study and data synthesis. Acta Obstet Gynecol Scand 2010;89:1162-7.  Back to cited text no. 25
Higgins L, Vause S, Tower C. Cytomegalovirus infection in association with early onset pre-eclampsia. BMJ Case Rep 2010;2010:bcr0320102803.  Back to cited text no. 26