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SUBPOPULATIONS OF T-LYMPHOCYTES IN ENDOMETRIUM IN PATHOGENESIS OF MISSED AND SPONTANEOUS ABORTIONS
Abstract
Background. Rate of early miscarriages is about 10-15% worldwide, and immune causes can play an important role in their pathogenesis. Normally Th2 lymphocytes is predominant subpopulation during early stages of pregnancy, while Th1 lymphocytes, which provide activation of cell immunity, are decreased. Regulatory T-lymphocytes (Treg, Th3) maintain tolerance to self-antigens and suppress excessive inflammatory response and also may be involved in pathogenesis of miscarriages. Th17 lymphocytes (Th17) play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces, but also can participate in autoimmune reactions. The role of subpopulations of T cells, especially Treg and Th17, in pathogenesis of miscarriages is not well known. Methods. Endometrial tissue of 22 patients with missed abortions, 22 patients with spontaneous abortions and 57 patients of control group (patents with progressive pregnancy, admitted for medical abortions) in 6-10 weeks of gestation was taken by uterine abrasion. Patients with severe extragenital diseases, endocrine disorders and aniphospholipid syndrome were excluded from research. Expression of mRNA of CD4, CD25, as well as Tbet and STAT4 (markers of Th1 lymphocytes), FoxP3 (marker of Treg lymphocytes), STAT3 (marker of Th17 lymphocytes) were estimated by quantitative PCR. Statistical analysis was performed by Mann-Whitney test using Statistica 6,0 (Statsoft, USA). Results. Expression of mRNA of CD25 and STAT4 (marker of Th1) was significantly higher in patients with missed abortion (5,6-fold and 88,5-fold accordingly) compared with control group (progressive pregnancy of early stage). Patients with missed abortions had no differences of mRNA expression of Tbet, FoxP3 and STAT3 in endometrium compared with control group. Expression of mRNA of Tbet (marker of Th1 lymphocytes) in endometrium in patients with spontaneous miscarriages was 2,8-fold higher, than in control group.. FoxP3 (marker of Treg) in patients with spontaneous miscarriages was 2,5-fold higher, than in control group. Expression of CD4 and STAT3 (marker of Th17 lymphocytes) had no differences in patients with missed and spontaneous abortions and control group. Conclusions. In patients with missed abortion significant mRNA increase of CD25 (marker of CD4+ T-lymphocytes) and STAT4 (marker of Th1 lymphocytes) was observed. In patients with spontaneous abortion increase of Tbet (marker of Th1 lymphocytes) and FoxP3 (marker of regulatory T-lymphocytes) were discovered. Expression of STAT3 (marker of Th17) didn't have significant difference in patients with missed and spontaneous abortions and the control group. Supported by Grant of President of Russian Federation MD-2326.2017.7.
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