• Serologic status, lymphocyte subsets and the system of TNF-receptors in CMV-infected pregnant women

Serologic status, lymphocyte subsets and the system of TNF-receptors in CMV-infected pregnant women

PERINATOLOGIYA I PEDIATRIYA. 2017.1(69):39-45; doi 10.15574/PP.2017.69.39

Serologic status, lymphocyte subsets and the system of TNF-receptors in CMV-infected pregnant women

Chernyshov V. P., Radysh T. V., Тоlkach S. M., Pisareva S. P.

SI «Institute of Pediatrics, Obstetrics and Gynecology of NAMS of Ukraine», Kyiv

Purpose — to study immune status in CMV-infected pregnant women according to their detailed serologic status.

Materials and methods. Serologic diagnostic method was used to determine IgM, level and avidity of IgG antibodies to CMV. ELISA was used for measurement level of TNF and TNF soluble receptors I and II. Lymphocyte subset analysis was carried out with flow cytometry. A total of 279 CMV seropositive women were examined at 6-12 weeks gestation.

Results. The majority of cases (18%) of low avidity CMV IgG were found among women with positive IgM and low IgG level. The low avidity antibodies were also detected in 7% of women with positive IgM and medium IgG level, and only 1% of patients with negative IgM and high IgG level. Аvidity of IgG antibodies inversely correlated with IgM positivity (r=-0.62; p<0.05) and directly correlated with IgG level (r=0.75; p<0.05). IgM positive women with low avidity and low IgG level hаd low level of CD3+, CD3+CD4+ lymphocyte, high level of NK, CD8 positive NK and CD3+CD56+ lymphocytes. They also showed increased TNF concentration and decreased level of TNF soluble receptors of both types. High numbers of NK, CD8 positive NK, CD3+CD56+ cells and increased TNF level were found in IgM positive women with medium avidity and medium IgG level. IgM negative women with high avidity and high IgG level showed high level of CD3+CD56+ cells only.

Conclusions. Serologic status of newly CMV infection (low IgG avidity plus low IgG level plus IgM positivity) and serologic status of CMV reactivation (medium IgG avidity plus medium IgG level plus IgM positivity) in pregnant women associate with NK, NKT-cells and TNF activation. Newly CMV infection and virus reactivation pregnant women causes immune status that put a pregnancy at risk.

Key words: cytomegalovirus infection, pregnancy, serologic status, avidity, lymphocytes subsets, natural killer, NK-like T-cells, tumours necrosis factor.

References

1. Vodyanik MA, Chenyshov VP, Omelchenko LI, Kutsenko EV. 2001. The use of monoclonal antibodies in cooperative enzyme immunoassay for the determination of human tumor necrosis factor. Ukraine Biochemical Journal. 73(6): 77-83.

2. Cheshik SG, Kisteneva LB. 2016. Human cytomegalovirus infection and spontaneous abortion in pregnant women of I and II trimester. Vopr Virusol. 61(2): 74-8. PMid:27451499

3. Chernyshov VP, Vodyanik MA, Pisareva SP. 2005. Lack of soluble TNF-receptors in women with recurrent spontaneous abortion and possibility for its correction. Am J Reprod Immunol. 54(5): 284-291. https://doi.org/10.1111/j.1600-0897.2005.00308.x; PMid:16212650

4. Pera A, Vasudev A, Tan C, Kared H, Solana R, Larbi A. 2016. CMV induces expansion of highly polyfunctional CD4+ T cell subset coexpressing CD57 and CD154. J Leukoc Biol. 2016 Aug 26; pii: jlb.4A0316-112R. doi 10.1189/jlb.4A0316-112R

5. Pachnio A, Ciaurriz M, Begum J, Lal N, Zuo J, Beggs A, Moss P. 2016. Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium. PLoS Pathog. 8; 12(9): e1005832. doi 10.1371/journal.ppat.1005832

6. Lissauer D, Choudhary M, Pachnio A, Goodyear O, Moss PA, Kilby MD. 2011. Cytomegalovirus sero positivity dramatically alters the maternal CD8+ T cell repertoire and leads to the accumulation of highly differentiated memory cells during human pregnancy. Hum Reprod. 26(12): 3355-3365. https://doi.org/10.1093/humrep/der327.

7. Van de Berg PJ, Yong SL, Remmerswaal EB, van Lier RA, ten Berge IJ. 2012. Cytomegalovirus-induced effector T cells cause endothelial cell damage. Clin Vaccine Immunol. 19: 772–779. https://doi.org/10.1128/CVI.00011-12

8. Nozawa N, Fang-Hoover J, Tabata T, Maidji E, Pereira L. 2009. Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream. J Clin Virol. 46 Suppl 4: S58-63. https://doi.org/10.1016/j.jcv.2009.10.004

9. Zhou Y, Bian G, Zhou Q, Gao Z, Liao P, Liu Y, He M. 2015.Detection of cytomegalovirus, human parvovirus B19, and herpes simplex virus-1/2 in women with first-trimester spontaneous abortions. J Med Virol. 87(10): 1749-1753. https://doi.org/10.1002/jmv.24218

10. Dons'koi BV. 2014. Accentuated hypo- and hyper-NK lymphocyte CD8 expression is a marker of NK subsets' misbalance and is predictive for reproductive failures. Immunobiology. 220(5): 649-55.  https://doi.org/10.1016/j.imbio.2014.11.015

11. Pievani A, Borleri G, Pende D, Moretta L, Rambaldi A, Golay J, Introna M. 2011. Dual-functional capability of CD3+CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity. Blood. 118(12):3301-10. https://doi.org/10.1182/blood-2011-02-336321

12. Hassouneh F, Campos C, López-Sejas N, Alonso C, Tarazona R, Solana R, Pera A. 2016. Effect of age and latent CMV infection on CD8+ CD56+ T cells (NKT-like) frequency and functionality. Mech Ageing Dev. 158(2): 38-45. https://doi.org/10.1016/j.mad.2015.12.003

13. Golic M, Luft FC, Dechend R. 2016. Tumor Necrosis Factor-α, Uterine Natural Killer Cells, and Pregnancy. Hypertension. 68(5): 1108-1109. https://doi.org/10.1161/HYPERTENSIONAHA.116.08028

14. Kalagiri RR, Carder T, Choudhury S, Vora N, Ballard AR, Govande V, Drever N, Beeram MR, Uddin MN. 2016. Inflammation in Complicated Pregnancy and Its Outcome. Am J Perinatol. 33(14): 1337-1356. https://doi.org/10.1055/s-0036-1582397

15. Lee SK, Kim JY, Han AR, Hur SE, Kim CJ, Kim TH, Cho BR, Han JW, Han SG, Na BJ, Kwak-Kim J. 2016. Intravenous Immunoglobulin G Improves Pregnancy Outcome in Women with Recurrent Pregnancy Losses with Cellular Immune Abnormalities. Am J Reprod Immunol. 75(1): 59-68.  https://doi.org/10.1111/aji.12442

16. Sonoyama A, Ebina Y, Morioka I, Tanimura K, Morizane M, Tairaku S, Minematsu T, Inoue N, Yamada H. 2012. Low IgG avidity and ultrasound fetal abnormality predict congenital cytomegalovirus infection. J Med Virol. 84(12): 1928-1933. https://doi.org/10.1002/jmv.23387

17. Vieira Braga FA, Hertoghs KM, van Lier RA, van Gisbergen KP. 2015. Molecular characterization of HCMV-specific immune responses: Parallels between CD8(+) T cells, CD4(+) T cells, and NK cells. Eur J Immunol. 45(9): 2433-2445. https://doi.org/10.1002/eji.201545495.

18. Nakase H, Herfarth H. 2016. Cytomegalovirus Colitis, Cytomegalovirus Hepatitis and Systemic Cytomegalovirus Infection: Common Features and Differences. Inflamm Intest Dis. 1(1): 15-23. https://doi.org/10.1159/000443198

19. Drew RJ, Stapleton P, Abu H, Healy E, Ferguson W, De Gascun C, O'Gorman J, Eogan M. 2015. Pregnancy outcomes of mothers with detectable CMV-specific IgM antibodies: a three-year review in a large Irish tertiary referral maternity hospital. Infect Dis Obstet Gynecol. 2015 (2015); ID 218080: 5 pages. https://doi.org/10.1155/2015/218080

20. Prince HE, Lapé-Nixon M. 2014. Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy. Clin Vaccine Immunol. 21(10):1377-1384. https://doi.org/10.1128/CVI.00487-14

21. Pusztai R, Lukácsi A, Kovács I. 2004. Mother-to-fetus transmission of cytomegalovirus. A review. Acta Microbiol Immunol Hung. 51(4): 385-401. https://doi.org/10.1556/AMicr.51.2004.4.1; PMid:15704329

22. Zhang Q, Liu XY, Zhang T, Zhang XF, Zhao L, Long F, Liu ZK, Wang EH. 2015. The dual-functional capability of cytokine-induced killer cells and application in tumor immunology. Hum Immunol. 76(5): 385-91. https://doi.org/10.1016/j.humimm.2014.09.021

23. Welten SP, Redeker A, Toes RE, Arens R. 2016. Viral Persistence Induces Antibody Inflation without Altering Antibody Avidity. J Virol. 90(9): 4402-4411. https://doi.org/10.1128/JVI.03177-15