02Mar 2018

CORRELATION BETWEEN INTERLEUKIN 17 AND TRANSFORMING GROWTH FACTOR BETA WITH HABITUAL ABORTION IN WOMEN INFECTED WITH CYTOMEGALOVIRUS.

  • Department of Clinical Laboratory Sciences, College of Pharmacy, AL-Mustansiriyah University. Baghdad, Iraq.
  • Kamal Al-Samarraee Teaching Hospital for Infertility and IVF.
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

Background: Interleukin 17 and transforming growth factor beta (TGF-β) are known with their effect on immune cells, and play a key role in the pathogenesis of some cell-mediated diseases, such as autoimmune diseases and cancer. Recurrent pregnancy loss (RPL) is a challenging field in generative medicine, the etiology of RPL is still not fully understood, and the knowledge regarding guides-based diagnostic and treatment are limited. Aim of study: The aim of this study was to investigate the the role of Interleukin 17 (IL17) and transforming growth factor beta (TGFβ) to CMV immunoglobulin in RPL in Iraqi patients infected with Cytomegalovirus (CMV), and to correlate them with RPL status, compared to the healthy control. Patients and methods: This study included 88 pregnant women, 37 women represented the healthy control, where no history of recurrent abortion. 24 patients were with two or more recurrent abortion, and 27 patients had a single abortion. The sera levels of IL17, TGFβ, and anti-CMV IgG, IgM were measured in blood patients by the enzyme-linked immunosorbent assay (ELISA). Results: The results revealed high levels of anti-CMV IgG in RPL patients compared to the healthy control (83.3%, 96.3% and 56.8% respectively; (p<0.001). While no significant difference was noted in levels of IgM anti-CMV, IL17 and TGFβ among the studied groups (p<0.001). Conclusion: There is a strong correlation between elevated anti-CMV IgG and RPL. However, IgM anti-CMV IL17 and TGFβ were correlated directly with in RSL patients compared with healthy control.


  1. Ahmed Z.K., Salman, Z.Q. (2014).Quantitative Detection of Human Cytomegalovirus (HCMV) Gene in Iraqi Women with Pregnancy Associated Problems. Iraqi Journal of Biotechnology, vol.13, No.1, 30-38.
  2. Aljumaili, Z.K., Alsamarai, A.M., Najem, W.S.:(2014).Cytomegalovirus seroprevalence in women with bad obstetric history in Kirkuk, Iraq. J Infect Public Health;7(4):277-88.
  3. Al-Jiffri, O., Al-Sharif, F. M. and El-Sayed , Z. M.:(2013). Seroprevalence of Cytomegalovirus among Donors and Other Investigated Groups . Intl. J. Microbial. Res. 4(1) :1?8.
  4. Cannon, M.J., Schmid, D.S., Hyde, T.B. (2010).Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 20(4):202-13.
  5. Darmochwal-Kolarz, D., Michalak, M., Kolarz, B., Monika Przegalinska-Kalamucka.(2017). The Role of Interleukin-17, Interleukin-23, and Transforming Growth Factor-β in Pregnancy Complicated by Placental Insufficiency. BioMed Research International.vol.2017, Article ID 6904325, 5 pages.
  6. Darmochwal-Kolarz, D., Kludka-Sternik ,M., Tabarkiewicz , J. (2012).?The predominance of Th17 lymphocytes and decreased number and function of Treg cells in preeclampsia,? Journal of Reproductive Immunology, vol. 93, no. 2, pp. 75?81,
  7. Duff,P. A (2007).thoughtful algorithm for the accurate diagnosis of primary CMV infection in pregnancy. Am J Obstet Gynecol March, pp. 196-197.
  8. Fischer, A.:( 2008).Human immunodeficiency: connecting STAT3, Th17 and human mucosal immunity. Immunol Cell Biol;86:549?51.
  9. Ford, H. B; Schust D. J.(2009). Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy. Rev Obstet Gynecol. 2(2): 76?83.
  10. Fowler, K.B.; Stagno, S.; Pass, R.F.; Britt, W.J.; Boll, T.J.; Alford, C.A. (1992).The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med;326:663-667.
  11. Gaffen, S. L. (2009). ?Structure and signalling in the IL-17 receptor family,? Nature Reviews Immunology, vol. 9, no. 8, pp. 556?567.
  12. Gaytant, M.A., Rours, G.I., Steegers, E.A., Galama, J.M., Semmekrot, B.A.(2003).Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature. Eur J Pediatr. 162(4):248-53.
  13. Giannubilo, S.R., Landi, B., Pozzi, V. (2012).The involvement of inflammatory cytokines in the pathogenesis of recurrent miscarriage. Cytokine 2012;58:50?6.
  14. Happel, K. I., Dubin, P. J., Zheng, M. (2005). Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae, The Journal of Experimental Medicine. 202, no. 6, pp. 761?769.
  15. Hananchi, N. ,Marzouk, M. , Harrabi, I. , Ferjani, A. and Ksouri, Z.:(2011). Seroprevalence of rubella virus, varicella zoster virus, cytomegalovirus and parvovirus B19 among pregnant women in the Sousse region, Tunisia. Bull. Soc. Pathol. Exot. 104 :62 - 67.
  16. Harrington, L.E., Hatton, R.D., Mangan, P.R,:(2005). Interleukin 17- producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol;6:1123?32.
  17. Hazell, S.L. (2007).?Clinical utility of avidity assays.?Expert Opin. Med. Diagn.1:511?519. 10.1517/17530059.1.4.511.
  18. Hussan,B.M.(2013).Study the prevalence of ACL,APL,CMV,HSV, Rubella and Toxoplasma gondii in aborted women in Baghdad. Medical Journal of Babylon.10 (2) :455-464.
  19. Huang, W. L. N, Fidel P. L, Schwarzenberger, P.(2004). ?Requirement of interleukin-17A for systemic anti-Candida albicans host defines in mice,? Journal of Infectious Diseases, vol. 190, no. 3, pp. 624?631.
  20. Ito, M., Nakashima, A., Hidaka, T.(2010). ?A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour,? Journal of Reproductive Immunology, vol. 84, no. 1, pp. 75?85.
  21. Kriel, R.L., Gates, G.A., Wulff, H., Powell, N., Poland, J.D., Chin, T.D. (1970). Cytomegalovirus isolations associated with pregnancy wastage. Am J Obstet Gynecol.15; 106(6):885-92.
  22. Kuwabara, T., Ishikawa, F., Kondo, M., and Kakiuchi, T.(2017). The Role of IL-17 and Related Cytokines in Inflammatory Autoimmune Diseases. Mediators of Inflammation. Article ID 3908061, 11 pages.
  23. Letterio, J. J. and? A. B. (1998). ?Regulation of immune responses by TGF-β,? Annual Review of Immunology, vol. 16, pp. 137?161.
  24. Li, M.O., Wan, Y.Y., Sanjabi, S., Robertson, A.K., Flavell, R.A. (2006).Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 24:99-146.
  25. Liu, Y.S., Wu, L., Tong, X.H.:(2011). Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol;65:503?11.
  26. Macklon, N.S., Geraedts, J.P.M., Fauser, B.C.J.M. (2002).Conception to ongoing pregnancy: the ?black box? of early pregnancy loss. Hum Reprod Update.8:333?343.
  27. Nakashima, A., Ito, M., Shima, T. Bac, N. D., Hidaka, T. and Saito, S. (2010). ?Accumulation of IL-17-positive cells in decidua of inevitable abortion cases,? American Journal of Reproductive Immunology, vol. 64, no. 1, pp. 4?11.
  28. Najafi, S, Hadinedoushan, H., Eslami, G. (2014). Association of IL-17A and IL-17 F gene polymorphisms with recurrent pregnancy loss in Iranian women. J Assist Reprod Genet .31:1491?1496. DOI 10.1007/s10815-014-0294-0.
  29. Naundorf, S., Schro?der, M., Ho? flich, C.:(2009). IL-10 interferes directly with TCR-induced IFN-gamma but not IL-17 production in memory T cells. Eur J Immunol;39:1066?77
  30. Nigro, G., Adler,S.P.(2011).Cytomegalovirus infections during pregnancy. Curr Opin Obstet Gynecol. 23(2):123-8.
  31. Nigro, G.(2009). Maternal?fetal cytomegalovirus infection: from diagnosis to therapy. J Matern Fetal Neonatal Med;22:169?174.
  32. Odland, J., Irina, I.V., Ivaneev, M.D.:(2001). Seropositivity of cytomegalovirus, parvovirus and rubella in pregnant women and recurrent aborters in Leningrad County, Russia. Acta Obstet Gynecol Scand; 80: 1025?1029.
  33. Ozkan, Z.S., Devecı, D., Sımsek, M., :(2014).What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?, The Journal of Maternal-Fetal & Neonatal Medicine. 28:3, 324-328, DOI: 10.3109/14767058.2014.916676.
  34. Pass, R.F., Anderson, B.:(2014). Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection. J Pediatric Infect Dis Soc; 3(Suppl 1): S2?S6.
  35. Raghupathy, R., Makhseed, M., Azizieh, F, :(2000).Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod;15: 713?18.
  36. Sadik, S., Fatima, H., Jamil, K., Patil, C.:(2012). Study of TORCH profile in patients with bad obstetric history. Biology and Medicine, 4 (2): 95-101.
  37. Saito, S., Nakashima A, Shima T, Ito M.:( 2010). Th1 ⁄ Th2 ⁄ Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol; 63: 601?610. doi:10.1111/j.1600-0897.2010.00852.x
  38. Sherkat, R. , Meidani, M., Zarabian, H., Rezaei, A., and Gholamrezaei, (2014). Seropositivity of cytomegalovirus in patients with recurrent pregnancy loss. J Res Med Sci. 19(Suppl 1): S22?S25.
  39. Stein, O., Sheinberg, B., Schiff, E., :(1997).Prevalence of antibodies to cytomegalovirus in a parturient population in Israel. Isr J Med Sci; 33: 53?8.
  40. Stephenson, M.(1996). Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril.66:24?29.
  41. Walshe, T. E., Saint-Geniez. M., Maharaj, A. S. R., Sekiyama, E., Maldonado, A. E., and D'Amore, P. A.(2009).?TGF-β is required for vascular barrier function, endothelial survival and homeostasis of the adult microvasculature,? PLoS ONE, vol. 4, no. 4, Article ID e5149.
  42. Zaki, M.E., Goda, H. (2007). Relevance of Parvovirus B19, Herpes Simplex Virus 2, and Cytomegalovirus Virologic Markers in Maternal Serum for Diagnosis of Unexplained Recurrent Abortions. Arch Pathol Lab Med.131:956?960.

[Qasim mohammed banja, thamer mutlk, samah a. Jassam, mohamed kadum al-araji and qays ahmed al-kafaji. (2018); CORRELATION BETWEEN INTERLEUKIN 17 AND TRANSFORMING GROWTH FACTOR BETA WITH HABITUAL ABORTION IN WOMEN INFECTED WITH CYTOMEGALOVIRUS. Int. J. of Adv. Res. 6 (Mar). 232-240] (ISSN 2320-5407). www.journalijar.com


Samah A Jassam BSc MSc PhD MRSB
Lecturer at the College of Pharmacy, AL-Mustansiriyah University. Baghdad, Iraq.

DOI:


Article DOI: 10.21474/IJAR01/6671      
DOI URL: https://dx.doi.org/10.21474/IJAR01/6671