Association of CD200 expression in paternal lymphocytes with female Th1/Th2 balance and pregnancy establishment at immunotherapy of recurrent spontaneous abortion

Abstract

We hypothesized that expression of transmembrane glycoprotein CD200 on paternal lymphocytes used for pre-gestational lymphocyte immunotherapy (LIT) of recurrent spontaneous abortion (RSA) can suppress the pro-inflammatory Th1-type immunity required for successful implantation. To reveal the association between CD200 expression, female immune background after LIT, and pregnancy establishment, we have performed this work. Pre-gestational alloimmunizations were given to 37 women using paternal peripheral blood leukocytes, combined with additional alloimmunizations in case of pregnancy. Lymphocyte phenotypes were determined by flow cytometry. Cytokines produced by mitogen-stimulated female peripheral blood cells were estimated by FlowCytomix™ technology. We have shown that 78.4% (29/37) of women became pregnant within 12 menstrual cycles after pre-gestational LIT. Pregnancy establishment depends on the intensity of CD200 expression, which is significantly higher on the CD200+ lymphocytes administered to women who later did not achieve pregnancy (P<.05). The expression of CD200 negatively correlates with the ratios of Th1/Th2 cytokines produced by female peripheral blood cells (P<.05) and positively correlates with the frequency of female circulating regulatory T cells after LIT (P<.05). The ROC analysis showed that the intensity of CD200 expression and the Th1/Th2 ratios are the significant predictors of pregnancy establishment after pre-gestational LIT (P<.05 and P<.01, respectively). Elevated CD200 expression on allogeneic lymphocytes most likely suppresses the pro-inflammatory Th1-type immunity needed for successful embryo implantation. Therefore, a personalized approach of LIT should be applied to avoid negative effects of such immunomodulation on pregnancy establishment.