The Role of CD28R Gene Variants in Pregnancy Loss Among Females Infected with Human Herpes 2 Virus
DOI:
https://doi.org/10.54133/ajms.v9i1.2187Keywords:
CD28R, HSV2, PCR, Recurrent miscarriage, SequencingAbstract
Background: Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus from the uterus before it is capable of survival. A co-stimulation molecule, CD28's aberrant expression can control T-cell activation and influence the strength of the immunological response. Particularly if obtained during pregnancy, the sexually transmitted infection known as herpes simplex virus type 2 (HSV-2) may be linked to spontaneous abortion. Objective: To investigate the effect of CD28R gene polymorphism as well as HSV2 infection in females suffering from recurrent miscarriage (RM). Methods: This case-control study involved a total of 200 placental tissue samples, with 100 obtained from female patients experiencing recurrent miscarriage (RM) and the remaining 100 from placentas exhibiting unremarkable pathological changes, serving as an apparently healthy control group with normal vaginal delivery. Polymerase chain reaction (PCR) was employed to detect HSV-2 DNA sequences, while Sanger sequencing was used to identify polymorphisms in the CD28R gene. Results: Recurrent miscarriage patients were older on average than the control group, which appeared to be in good health. A substantial positive association was found between mother age, the number of abortions, the number of participants, and the week of the abortion. 27% of the cases tested positive for HSV-2 DNA, according to PCR results, while 73% tested negative. Statistically significant differences were found among groups based on CD28R gene genotyping. Conclusions: Polymorphisms of the CD28R gene and presence of HSV-2 may be considered risk factors for recurrent abortion among Iraqi women.
Downloads
References
Misra M , Singh B , Mishra A. Co-stimulatory CD28 and transcription factor NFKB1 gene variants affect idiopathic recurrent miscarriages. J Hum Genet. 2016;61(12):1035–1041. doi: 10.1038/jhg.2016.100.
Wang G, Sun J. Interactive effects of Snps located Within CD28/B7 pathway and environment on susceptibility to recurrent spontaneous abortion. Cell Physiol Biochem. 2017;43(6):2185-2199. doi: 10.1159/000484297. DOI: https://doi.org/10.1159/000484297
Guan D, Sun W, Gao M, Chen Z, Ma X. Immunologic insights in recurrent spontaneous abortion: Molecular mechanisms and therapeutic interventions. Biomed Pharmacother. 2024;177:117082. doi: 10.1016/j.biopha.2024.117082 DOI: https://doi.org/10.1016/j.biopha.2024.117082
Zhang S, Audard V, Fan Q, Pawlak A, Lang P, Sahali D. Immunopathogenesis of idiopathic nephrotic syndrome. Contrib Nephrol. 2011;169:94-106. doi: 10.1159/000313947. DOI: https://doi.org/10.1159/000313947
Gan L, Jia R, Zhou L, Guo J, Fan M. Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine. PLoS One. 2014;9(9):108892. doi: 10.1371/journal.pone.0108892. DOI: https://doi.org/10.1371/journal.pone.0108892
Li X, Dai J, Yuan H, Zhang X. Expression and role of CD40/CD40L and B7-1/CD28 interaction in folic acid-induced nephropathy. Chinese J Nephrol. 2005;21(9):534-537.
Eblen AC, Gercel-Taylor C, Shields LB, Sanfilippo JS, Nakajima ST, Taylor DD. Alterations in humoral immune responses associated with recurrent pregnancy loss. Fertil Steril. 2000;73(2):305-313. doi: 10.1016/s0015-0282(99)00505-1. DOI: https://doi.org/10.1016/S0015-0282(99)00505-1
Misra MK, Singh B, Mishra A, Agrawal S. Co-stimulatory CD28 and transcription factor NFKB1 gene variants affect idiopathic recurrent miscarriages. J Hum Genet. 2016;61(12):1035–1041. doi: 10.1038/jhg.2016.100. DOI: https://doi.org/10.1038/jhg.2016.100
Holt MP, Punkosdy GA, Glass DD, Shevach EM. TCR signaling and CD28/CTLA-4 signaling cooperatively modulate T regulatory cell homeostasis. J Immunol. 2017;198(4):1503–1511. doi: 10.4049/jimmunol.1601670. DOI: https://doi.org/10.4049/jimmunol.1601670
Gupta R, Warren T, Wald A. Genital herpes. Lancet. 2007;370(9605):2127-2137. doi: 10.1016/S0140-6736(07)61908-4. DOI: https://doi.org/10.1016/S0140-6736(07)61908-4
Xu F. Sternberg MR, Kottiri BJ, McQuillan GM, Lee FK, Nahmias AJ. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006;296(8):964-973. doi: 10.1001/jama.296.8.964. DOI: https://doi.org/10.1001/jama.296.8.964
Dakhil AS. Role of Epstein Barr virus (EBV) in human females with breast cancer. Iraqi J Biotechnol. 2017l;9(7):1173-1177.
Kriebs JM. Understanding herpes simplex virus: transmission, diagnosis, and considerations in pregnancy management. J Midwif Women Health. 2008;53(3):202-208. doi: 10.1016/j.jmwh.2008.01.010. DOI: https://doi.org/10.1016/j.jmwh.2008.01.010
Sauerbrei A, Wutzler P. Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Med Microbiol Immunol. 2007;196(2):95-102. doi: 10.1007/s00430-006-0032-z. DOI: https://doi.org/10.1007/s00430-006-0032-z
Popinchalk A, Sedgh G. Trends in the method and gestational age of abortion in high-income countries. BMJ Sex Reprod Health. 2019;45(2):95-103. doi: 10.1136/bmjsrh-2018-200149. DOI: https://doi.org/10.1136/bmjsrh-2018-200149
Dellicour S, Aol G, Ouma P, Yan N, Bigogo G, Hamel MJ, et al. Weekly miscarriage rates in a community-based prospective cohort study in rural western Kenya. BMJ Open. 2016;6(4):e011088. doi: 10.1136/bmjopen-2016-011088. DOI: https://doi.org/10.1136/bmjopen-2016-011088
Kimberlin DW. Herpes simplex virus infections of the newborn. Semin Perinatol. 2007;31(1):19-25. doi: 10.1053/j.semperi.2007.01.003. DOI: https://doi.org/10.1053/j.semperi.2007.01.003
Stanberry LR, Kliegman RM, Behrnan RE, Jenseon HB, Stanton BF, (Eds.), Herpes simplex virus. In: Nelson Text Book of Pediatrics. 2007.18 (249):1360-1379.
Robb JA, Benirschke K, Barmeyer R. Intrauterine latent herpes simplex virus infection in Spontaneous abortion. Hum Pathol. 1986;17(12):1196-209. doi: 10.1016/s0046-8177(86)80561-5. DOI: https://doi.org/10.1016/S0046-8177(86)80561-5
Chow SS, Craig ME, Jacques CF, Hall B, Catteau J, Munro SC, et al. Correlates of placental infection with cytomegalovirus, parvovirus B19 or human herpes virus 7. J Med Virol. 2006;78(6):747-756. doi: 10.1002/jmv.20618. DOI: https://doi.org/10.1002/jmv.20618
Rhagupathy R. Maternal anti-placental cell-mediated reactivity and spontaneous abortions. Am J Reprod Immunol. 1997;37(6):478-484. doi: 10.1111/j.1600-0897.1997.tb00263.x. DOI: https://doi.org/10.1111/j.1600-0897.1997.tb00263.x
Kwak JY, Beer AE, Kim SH, Mantouvalos HP. Immunopathology of the implantation site utilizing monoclonal antibodies to natural killer cells in women with recurrent pregnancy losses. Am J Reprod Immunol. 1999;41(1):91-98. doi: 10.1111/j.1600-0897.1999.tb00080.x. DOI: https://doi.org/10.1111/j.1600-0897.1999.tb00080.x
Bujko M, Sulovic V, Zivanovic V, Dotlić R. Herpes simplex virus infection in women with previous spontaneous abortion. J Perinat Med. 1988;16(3):193-196. doi: 10.1515/jpme.1988.16.3.193. DOI: https://doi.org/10.1515/jpme.1988.16.3.193
Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis. 2002;186(1):3-28. doi: 10.1086/343739. DOI: https://doi.org/10.1086/343739
Garcon F, Patton DT, Emery JL, Hirsch E, Rottapel R, Sasaki T, et al. CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. Blood. 2008;111(3):1464-1471. doi: 10.1182/blood-2007-08-108050. DOI: https://doi.org/10.1182/blood-2007-08-108050
Jin LP, Zhou YH, Wang MY, Zhu XY, Li DJ. Blockade of CD80 and CD86 at the time of implantation inhibits maternal rejection to the allogeneic fetus in abortion-prone matings. J Reprod Immunol. 2005;65(2):133-146. doi: 10.1016/j.jri.2004.08.009. DOI: https://doi.org/10.1016/j.jri.2004.08.009
Ling V, Gray GS, Keith JC, (Patent), Methods of preventing immune-mediated abortion by inhibiting a CD28- mediated costimulatory signal. US 2004/0126781 A1. Available at: https://patents.google.com/patent/US20040126781A1
Chen DP, Lin WT, Wang WT, Chiueh TS. The influence of CD28 gene polymorphism in transfusion reaction after transfusing leukoreduced blood components. J Clin Med. 2020;9(3):877. doi: 10.3390/jcm9030877. DOI: https://doi.org/10.3390/jcm9030877
Mikhaylichenko O, Bondarenko V, Harnett D, Schor IE, Males M, Viales RR, et al. The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription. Genes Dev. 2018;32:42–57. doi: 10.1101/gad.308619.117. DOI: https://doi.org/10.1101/gad.308619.117
Wang C, Gui Q, Zhang K. Functional polymorphisms in CD86 gene are associated with susceptibility to pneumonia-induced sepsis. APMIS. 2015;123(5):433-438. doi: 10.1111/apm.12364. DOI: https://doi.org/10.1111/apm.12364
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 )
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Published by Al-Rafidain University College. This is an open access journal issued under the CC BY-NC-SA 4.0 license (https://creativecommons.org/licenses/by-nc-sa/4.0/).
