Effect of immunocytotherapy on the state of the immune system of women with idiopathic habitual miscarriage

We aimed  for assessing effects of immunocytotherapy upon  the subpopulations of CD4⁺CD25^highFoxP3⁺ cellswithnaturalregulatoryactivityandactivatedTh17cellswiththeCD4⁺CD25^highRORγt⁺ phenotype, as well as in vitro production of cytokines in mitogen-stimulated cells from  peripheral blood  in the patients with idiopathic habitual miscarriage (IHM). The study group consisted of 33 patients with IHM who became pregnant after a pre-gestational alloimmunization. In 27 patients, the pregnancy was prolonged to the  full term  and  ended  with the  birth  of viable babies,  in six cases it was terminated before  12 weeks of gestation. Before  administration of immunocytotherapy (ICT), 19 patients were examined, of them  16 after alloimmunization outside of pregnancy, 17 at 5-6 and 8-9 weeks of pregnancy. Eleven patients were immunized at 12 weeks of pregnancy. In the control group,  12 fertile women  outside  pregnancy and 10 women  at 12 weeks of physiological pregnancy were examined. The proportion of FoxP3⁺ and RORγt⁺ cells with the CD4⁺CD25^high phenotype was evaluated among  T-lymphocytes from peripheral blood,  as well as content of proinflammatory cytokines (IFNγ,  TNFα, IL-1β, IL-2, IL-5, IL  -6,  IL-8, IL-12p70) and  anti-inflammatory factors  (IL-4, IL-10), as well as IL-17  amounts.

We have found  that,  following pre-gestational alloimmunization, the women  who lost this pregnancy, had a  low  level  of  FoxP3+Тregs that  suppress  pro-inflammatory Th17-dependent  reactions, however, without changing levels of activated Th17  cells (CD4⁺CD25^highRORγt⁺   lymphocytes). These  facts,  along  with  high in vitro production of IL-17  by peripheral blood cells at the terms of 5-6 weeks of gestation, suggest that,  after pre-gestational alloimmunization in women  with miscarriage, a predilection is formed  to pro-inflammatory cytokine production. However, at the 5-6 week-period, it is realized  not in the Th1 direction of, but towards Th17 response, and a low level of CD4⁺CD25^highRORγt⁺ cells may reflect an increased migration of Th17 cells from peripheral blood to the uterine endometrium.

Thus,  we have shown  the  effect of immunocytotherapy upon  subpopulational composition of peripheral blood  lymphocytes and  the  cytokine profile,  as well as upon  the  course  of first trimester and  outcomes of pregnancy in women  with idiopathic habitual miscarriage.

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