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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+CD25highphenotype 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.

Endometriosis is a common estrogen-dependent chronic disease in women of reproductive age; it is associated with dysregulation of the immune response, local inflammation, and increased formation of autoantibodies. The aim of the study was to investigate the profile of autoantibodies in women with endometriosis and to evaluate their diagnostic value using new modifications of enzyme immunoassay. In women with endometriosis of stage III-IV (n=39), a wide spectrum of autoantibodies was detected, mainly of class G, including antibodies to endometrial antigens (tropomyosin 3, tropomodulin 3), the enzyme α-enolase, steroid (estradiol, progesterone) and gonadotropic hormones. At the same time, the frequency of detection of IgG antibodies to tropomyosin 3, α-enolase, estradiol and human chorionic gonadotropin and their levels in patients with endometriosis were higher than in healthy women (n=26) (p0.05). IgG-antibodies to tropomyosin 3, α-enolase and estradiol were characterized by higher diagnostic value for endometriosis. The diagnostic value was significantly increased when these antibodies were combined: the AUC reached 0.875 [0.772-0.978] (p0.0001), the sensitivity and specificity were 83.3% each. Thus, autoantibodies to tropomyosin 3, α-enolase, and estradiol are promising for inclusion in the panel of biomarkers for non-invasive diagnosis of endometriosis.Éndometrioz iavliaetsia rasprostranennym éstrogen-zavisimym khronicheskim zabolevaniem zhenshchin reproduktivnogo vozrasta, kotoroe assotsiiruetsia s disreguliatsieĭ immunnogo otveta, mestnym vospalitel'nym protsessom i povyshennym obrazovaniem autoantitel. Tsel'iu dannogo issledovaniia bylo izuchit' s primeneniem novykh modifikatsiĭ immunofermentnogo analiza profil' autoantitel u zhenshchin c éndometriozom i otsenit' ikh diagnosticheskoe znachenie. U zhenshchin s naruzhnym genital'nym éndometriozom III-IV stadii (n=39) vyiavlen shirokiĭ spektr autoantitel preimushchestvenno klassa G, vkliuchaiushchiĭ antitela k éndometrial'nym antigenam (tropomiozinu 3, tropomodulinu 3), fermentu α-enolaze, steroidnym (éstradiolu, progesteronu) i gonadotropnym gormonam. Pri étom chastota vyiavleniia IgG-antitel k tropomiozinu 3, α-enolaze, éstradiolu i khorionicheskomu gonadotropinu cheloveka i ikh urovni u patsientok s éndometriozom byli vyshe, chem u zdorovykh zhenshchin (n=26) (p0,05). IgG-antitela k tropomiozinu 3, α-enolaze i éstradiolu kharakterizovalis' bolee vysokoĭ diagnosticheskoĭ znachimost'iu dlia éndometrioza. Pri kombinatsii dannykh antitel diagnosticheskaia znachimost' sushchestvenno povyshalas', znachenie AUC dostigalo 0,875 [0,772-0,978] (p0,0001), pokazateli chuvstvitel'nosti i spetsifichnosti sostavliali 83,3% kazhdyĭ. Takim obrazom, autoantitela k tropomiozinu 3, α-enolaze i éstradiolu iavliaiutsia perspektivnymi dlia vkliucheniia v panel' biomarkerov dlia neinvazivnoĭ diagnostiki éndometrioza.

The aim of this work was to characterize phenotypically peripheral blood T- and NK lymphocytes expressing an early marker of activation, CD69, and assess the significance of CD69 expression for predicting pregnancy outcome in women with idiopathic reccurent pregnancy loss (IRP) before and after immunocytotherapy (ICT). The study group consisted of 36 patients with IRP who became pregnant after pre-gestational allimmunization, in 30 patients the pregnancy was prolonged to the full term and ended with the birth of a viable baby, in 6 - it was terminated before 12 weeks of gestation. In the control group, 15 fertile women outside pregnancy and 11 women at 12 weeks of physiological pregnancy were examined. Assessment of the CD69 expression in women with prolonged pregnancy revealed the absence of significant differences with the control group in the content and proportion of activated lymphocytes (CD69+). In women with aborted pregnancy after pre-gestational ICT, an increase in the number of almost all analyzed lymphocyte subpopulations responding to the activation stimulus, with a clear tendency to increase the proportion of activated T- but not NK-lymphocytes was found. At 5-6 weeks, the proportion of activated lymphocytes among a subpopulation of cytotoxic T-lymphocytes (CD3+CD8+/CD3+CD8+CD69+) in these women was significantly higher than in women with prolonged pregnancy, which confirms the leading role of effector cytotoxic T-lymphocytes in rejection reactions. Thus, the studies showed the promise of evaluating the expression of the early activation marker CD69 as an additional laboratory criterion for the personable appointment of immunocytotherapy to women with a common reccurent pregnancy loss.Tsel' dannoĭ raboty zakliuchalas' v fenotipicheskoĭ kharakteristike T- i NK-limfotsitov perifericheskoĭ krovi, ékspressiruiushchikh ranniĭ marker aktivatsii CD69, i otsenke znachimosti étogo markera dlia prognoza iskhoda beremennosti u zhenshchin s idiopaticheskim privychnym vykidyshem (IPV) do i posle provedeniia immunotsitoterapii (ITsT). Gruppu issledovaniia sostavili 36 patsientok s IPV, kotorye zaberemeneli posle predgestatsionnoĭ alloimmunizatsii, u 30 patsientok beremennost' prolongirovana do donoshennogo sroka i zavershilas' rozhdeniem zhiznesposobnogo rebenka, u 6 — prervalas' do 12 nedel' gestatsii. V kontrol'noĭ gruppe obsledovano 11 zhenshchin v 12 nedel' fiziologicheskoĭ beremennosti. Otsenka ékspressii CD69 u zhenshchin s prolongirovannoĭ beremennost'iu vyiavila otsutstvie znachimykh razlichiĭ s kontrol'noĭ gruppoĭ po soderzhaniiu i dole aktivirovannykh limfotsitov (CD69+). U zhenshchin s prervavsheĭsia beremennost'iu posle predgestatsionnoĭ ITsT obnaruzheno uvelichenie kolichestva prakticheski vsekh analiziruemykh subpopuliatsiĭ limfotsitov, otvechaiushchikh na aktivatsionnyĭ stimul, s iarkoĭ tendentsieĭ k uvelicheniiu doli aktivirovannykh T-, no ne NK-limfotsitov. V 5-6 nedel' dolia aktivirovannykh limfotsitov sredi subpopuliatsii tsitotoksicheskikh T-limfotsitov (CD3+CD8+/CD3+CD8+CD69+) u étikh zhenshchin byla znachimo vyshe, chem u zhenshchin s prolongirovannoĭ beremennost'iu, chto podtverzhdaet vedushchuiu rol' v reaktsiiakh ottorzheniia ploda éffektornykh tsitotoksicheskikh T-limfotsitov. Takim obrazom, provedennye issledovaniia pokazali perspektivnost' otsenki ékspressii rannego aktivatsionnogo markera CD69 kak dopolnitel'nogo laboratornogo kriteriia dlia personifitsirovannogo naznacheniia ITsT zhenshchinam s privychnym vykidyshem.

Association between lymphocyte activation and formation of immune tolerance, as well as pregnancy outcome, in the case of immunocytotherapy (ICT) was studied in women with idiopathic recurrent pregnancy loss (IRPL). The content and phenotypic characteristics of activated T lymphocytes and NK cells were investigated in the peripheral blood of IRPL patients with different pregnancy outcomes (pregnancy prolongation to the full term and habitual miscarriage). The fraction of activated cells in the subpopulation of cytotoxic T lymphocytes (CD3+CD8+/CD3+CD8+CD69+) before ICT was significantly lower in women who lost the pregnancy. After ICT, the fraction of these cells during weeks 5-6 of pregnancy in woman with miscarriage was higher than in women with pregnancy prolonged to the full-term. Excessive content of activated cytotoxic lymphocytes can be a mechanism underlying impaired maternal immunotolerance to fetal alloantigens, which is a leading factor of early pregnancy loss. The obtained data confirm the involvement of activated Th17 cells and FOXP3+ Treg cells in the formation of tolerance to paternal antigens of the fetus. Comparison of the decrease in the fraction of CD4+CD25highRORγt+ lymphocytes at the early gestation period (5-6 weeks) and significant upregulation of the IL-17 production by in vitro stimulated whole blood cells in women with miscarriage with the same parameters in women with prolonged pregnancy suggested an imbalance between pro-inflammatory Th17 cells and Treg cells. No such imbalance in the content effector T lymphocytes was observed in women with the full-term pregnancy. Taken together, our data indicate an important role of gestational activation of lymphocytes in the formation of maternal immune response to fetal alloantigens necessary for the prolongation of pregnancy.

Objective: the elicitation of immune status changes in patients with benign ovarian tumors and reproductive function disorders.