Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2005; 51(2): 65-72

Immunopathophysiologic featuresof early pregnancy in womenwith a history of unexplainablepregnancy loss

Т.V. Radysh, V.P. Chernyshov

    Institute of Pediatrics, Obstetrics and Gynecology, Academyof Medical Science of Ukraine, Kyiv



Abstract

The lymphocyte subsets, activation marker expression and activity of ConA-treated lymphocytes have been studied in 58 patients with a history of unexplainable pregnancy loss (UPL) and 22 normal pregnant women (control) in 4-7 weeks of pregnancy. The increase of CD16/56+ cell level and CD4+/ CD8+ ratio and decrease of CD19+ cell level have been found in peripheral blood of UPL patients in comparison with control. The expression of HLA-DR was upregulated on CD3+ and CD8+ cells and the expression of CD25 was downregulated on CD3+, CD4+, CD8+, and CD16/56+ cells in UPL women. Ac- cording to correlation analysis results, low expression of CD25 was related to a low expression of CD8 on NK, high expres- sion of CD45RA on CD4+ helper cells, high expression of HLA-DR on CD8+ cytotoxic cells. High frequency of ConA- induced activation, low frequency of ConA-induced suppres- sion and low suppressive activity of ConA-induced lymphocyte were found in UPL patients compared to control. Conclusion: women with UPL have disorders in feto-maternal recognition in early pregnancy that led to a development of the inadequate immune response to fetus realized as a defect of NK activation, deficiency of T-cytotoxic cell limitation and memory helper cell generation, downregulation of TR cells and suppressor function.

Full text: (PDF, in Ukrainian)

References

  1. Осипов В.П., Лук’янова Е.М., Антипкин Ю.Г. и др.Методика статистической обработки медицинскойинформации в научных исследованиях. – К.: Планеталюдей, 2002. – 200 с.
  2. Рудакова Н.В. Порівняльна характеристика ефек-тивності різних методів терапії невиношуваннявагітності нез’ясованої етіології: Автореф. дис. ...канд. мед. наук. – К., 2003. – 23 с.
  3. Стукалова О.М. Диференційований підхід додіагностики та комплексної терапії невиношуваннявагітності. Автореф. дис. ... канд. мед. наук. – К., 2002. – 21 с.
  4. Aoki K., Kajiura S., Matsumoto Y. et al. Preconceptionalnatural-killer-cell activity as a predictor of miscarriage// Lancet. – 1995. – 345, № 8961. – P.1340–1342.
  5. Beer A.E., Kwak J.Y., Ruiz J.E. Immunophenotypicprofiles of peripheral blood lymphocytes in womenwith recurrent pregnancy losses and in infertile womenwith multiple failed in vitro fertilization cycles // Amer.J. Reprod. Immunol. – 1996. – 35, № 4. – P.376–382.
  6. Clark D.A., Coulam C.B., Daya S., Chaouat G. Unexplainedsporadic and recurrent miscarriage in the new millennium: acritical analysis of immune mechanisms and treatment //Hum. Reprod. Update. – 2001. – 7. – P. 501–511.
  7. Coulam C.B. Understanding the immunobiology of preg-nancy and applying it to treatment of recurrent preg-nancy loss // Early Pregnancy. – 2000. – 4. – P.19–29.
  8. Coulam C.B., Goodman C., Roussev R.G. et al. Sys-temic CD56+ cells can predict pregnancy outcome //Amer. J. Reprod. Immunol. – 1995. – 33. – P.40–46.
  9. 9. Cramer D.W., Wise L.A. The epidemiology of recurrentpregnancy loss // Semin. Reprod. Med. – 2000. – 18,№ 4. – P.331–339.
  10. 10. Emmer P.M., Nelen W.L., Steegers E.A. et al. Peripheralnatural killer cytotoxicity and CD56(pos)CD16(pos) cellsincrease during early pregnancy in women with a historyof recurrent spontaneous abortion // Hum. Reprod. – 2000. –15, № 5. – P.1163–1169.
  11. Griffith T.S., Brunner T., Fletcher S.M. Fas ligand-induced apoptosis as a mechanism of immune privi-lege // Science. – 1995. – 270. – P.1189–1192.
  12. Hill J.A., Choi B.C. Maternal immunological aspectsof pregnancy success and failure // J. Reprod. Fertil.Suppl. – 2000. – 55. – P.91–97.
  13. Kotlan B., Fulop V., Padanyi A. et al. High anti-paternalcytotoxic T-lymphocyte precursor frequencies in womenwith unexplained recurrent spontaneous abortions // Hum.Reprod. – 2001. – 16, № 6. – P.1278–1285.
  14. Kwak J.Y., Beaman K.D., Gilman-Sachs A. et al. Up-regulated expression of CD56+, CD56+/CD16+, andCD19+ cells in peripheral blood lymphocytes in preg-nant women with recurrent pregnancy losses // Amer.J. Reprod. Immunol. – 1995. – 34, № 2. – P.93–99.
  15. Lenardo M., Chan F.K.M., Hornung F. Maturelymphocyte apoptosis-immune regulation in a dynamicand unpredictable antigenic environment // Ann. Rev.Immunol. – 1999. – 17. – P.221–253.
  16. Li D., Zhu Y., Wang M. Immuno-epidemiologicalinvestigation of recurrent spontaneous abortion //Zhonghua Yi Xue Za Zhi. – 1998. – 78, № 2. – P.94–97.
  17. Lopez B.H.H., Vallejo B.J., Malvaez G.B. et al. Use ofa diagnostic prospective algorithm for patients withrecurrent Miscarriage // Ginecol. Obstet. Mex. – 1995. –63. – P.96–101.
  18. Mahmoud F., Abul H., Omu A. et al. Pregnancy-asso-ciated changes in peripheral blood lymphocyte sub-populations in normal Kuwaiti women // Gynecol.Obstet. Invest. – 2001. – 52, № 4. – P.232–236.
  19. 19. Makrydimas G., Plachouras N., Higueras M.T. et al.Maternal peripheral blood lymphocyte subpopulationsin normal and pathological pregnancies // Fetal Diagn.Ther. – 1994. – 9, № 6. – P.371–378.
  20. 20. Masuko-Hongo K., Hayashi K., Yonamine K. et al.Disappearance of clonally expanded T cells after allo-geneic leukocyte immunotherapy in peripheral bloodof patients with habitual abortion // Hum. Immunol. –2001. – 62, № 10. – P.1111–1121.
  21. Meeusen E.N., Bischof R.J., Lee C.S. Comparative T-cell responses during pregnancy in large animals andhumans // Amer. J. Reprod. Immunol. – 2001. – 46, №2. – P.169–179.
  22. Miller J.S., Oelkers S., Verfaillie C. Role of monocytesin the expansion of human activated natural killer cells// Blood. – 1992. – 80. – P.2221–2227.
  23. Mincheva-Nilsson L. Pregnancy and gamma/delta TTaking on the hard questions // Reprod. Biologyand Endocrinology. – 2003. – 1. – P.120–131.
  24. Morikawa M., Yamada H., Kato E.H. et al. NK cellactivity and subsets in women with a history of spon-taneous abortion. Cause, number of abortions, andsubsequent pregnancy outcome // Gynecol. Obstet.Invest. – 2001. – 52, № 3. – P.163–167.
  25. Psarra K., Kapsimali V., Tarassi K. et al. TCRgam-madelta + T lymphocytes in unexplained recurrentspontaneous abortions // Amer. J. Reprod. Immunol. –2001. – 45, № 1. – P.6–11.
  26. Seaman W.E. Natural killer cells and natural killer Tcells // Arthritis Rheum. – 2000. – 43. – P.1204–1217.
  27. Shevach E.M. CD4+ CD25+ suppressor T cells: morequestions than answers // Nat. Rev. Immunol. – 2002. –№ 2. – P.389–400.
  28. Siegel R.M., Fleisher T.A. The role of Fas and relateddeath receptors in autoimmune and other disease states // J. Allergy Clin. Immunol. – 1999. – 103. – P.729–738.
  29. 29. Szpakowski A., Malinowski A., Zeman K. et al. Theinfluence of paternal lymphocytes immunization onpercentage of peripheral blood CD16+/CD56+ cells inwomen with primary recurrent spontaneous abortion //Ginekol. Pol. – 2001. – 72, № 12. – P.1063–1068.
  30. 30. Taams L.S., Vukmanovic-Stejic M., Smith J. et al. Anti-T cell suppression by human CD4+CD25+regulatory T cells //Eur. J. Immunol. – 2002. – 32. –P.1621–1630.
  31. Verhasselt V., Vosters O., Beuneu C. et al. Induction ofFOXP3-expressing regulatory CD4pos T cells by hu-man mature autologous dendritic cells // Eur. J. Immu-nol. – 2004. – 34. – P.762–772.
  32. Wilczynski J., Sulowska Z., Malinowski A. et al. CD3-CD3+/HLA-DR+ cell levels and PHAstimulation of lymphocytes obtained from women withrecurrent spontaneous abortions and subjected topartner’s lymphocyte immunization // Arch. Immunol.Ther. Exp. (Warsz). – 1997. – 45, № 4. – P.289–294.
  33. Yamada H., Kato E.H., Kobashi G. et al. NK cell activ-ity in early pregnancy correlates with subsequent abor-tion with normal chromosomes in women with recurrentabortion // Amer. J. Reprod. Immunol. – 2001. – 46, №2. – P.132 –136.
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.