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

Abstract

We aimed for assessing effects of immunocytotherapy upon the subpopulations of CD4+CD25highFoxP3+ cellswithnaturalregulatoryactivityandactivatedTh17cellswiththeCD4+CD25highRORγt+ 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+CD25high 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+CD25highRORγt+ 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+CD25highRORγt+ 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.

Keywords

• habitual miscarriage
• immunocytotherapy
• cytokines
• foxp3+
• treg
• th17