TIME TO PREGNANCY AFTER PRE-GESTATIONAL ALLOGENEIC IMMUNOTHERAPY AND PERIPHERAL BLOOD CELL CYTOKINE PROFILE IN WOMEN WITH A HISTORY OF RECURRENT SPONTANEOUS ABORTION


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Abstract

An optimal ratio of inflammatory (Th1) and anti-inflammatory (Th2) immune responses is required for successful embryo implantation and subsequent fetal development. Allogenic lymphocyte immunization also referred to as cell immunotherapy (CIT) before conception and in the early stages of pregnancy, effectively corrects immunoregulation in women with recurrent spontaneous abortion. However, the time to pregnancy (TTP) after pre-gestational CIT varies significantly. Aim. To investigate the relationship between Th1/Th2 cytokine balance after pre-gestational CIT and the TTP in women with a history of recurrent spontaneous abortion. Materials and methods. The study included 37 women who underwent CIT as monotherapy. TTP was defined as the duration of time expressed in the number of menstrual cycles from contraception discontinuation until conception occurred. Production of pro-inflammatory (IFN-γ, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, IL-1β) and anti-inflammatory (IL-4, IL-5, IL-10) cytokines after mitogen-induced activation of maternal peripheral blood cells were analyzed by flow cytometry using FlowCytomix ™ kits (eBioscience). Results. In 22 (59.5%) women, pregnancy occurred within six menstrual cycles, and five (13.5%) women conceived between 7 to 12 menstrual cycles. Ten women (27%) failed to achieve pregnancy within 12 menstrual cycles. Compared to women with TTP ≤ 6 menstrual cycles, those with 6 < ТТР ≤ 12 menstrual cycles and who was unable to conceive had reduced Th1/Th2 cytokine ratio. Conclusion. The TTP after allogeneic immunotherapy may depend on the Th1/Th2 cytokine ratio.

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About the authors

Marina A. NIKOLAEVA

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: nikolaeva_ma@mail.ru
Dr. Bio. Sci., Leading Researcher at the Laboratory of Clinical Immunology Moscow, Russia

Alla S. AREFIEVA

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: arefeva.oparina4@gmail.com
Researcher at the Laboratory of Clinical Immunology Moscow, Russia

Elena O. STEPANOVA

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: elena2404.07@mail.ru
Junior Researcher at the Laboratory of Clinical Immunology Moscow, Russia

Elena L. GOLUBEVA

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_golubeva@oparina4.ru
Ph.D., Clinical Pathologist at the Laboratory of Clinical Immunology Moscow, Russia

Valentina V. VTORUSHINA

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: vtorushina@inbox.ru
Ph.D., Clinical Pathologist at the, Laboratory of Clinical Immunology Moscow, Russia

Nana K. TETRUASHVILI

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: tetrauly@mail.ru
Dr. Med. Sci., Head of the 2nd Obstetric Department of Pregnancy Pathology Moscow, Russia

Lyubov V. KRECHETOVA

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: l_krechetova@oparina4.ru
Dr. Med. Sci., Head of Laboratory of Clinical Immunology Moscow, Russia

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