Laboratory of Clinical Immunology, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, Moscow, Russia.
Department of Pregnancy Loss Prevention and Therapy, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, Moscow, Russia.
Am J Reprod Immunol. 2021 Mar;85(3):e13355. doi: 10.1111/aji.13355. Epub 2020 Oct 18.
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.
我们假设用于复发性自然流产（RSA）的前妊娠淋巴细胞免疫治疗（LIT）的父系淋巴细胞上表达的跨膜糖蛋白 CD200 可以抑制成功植入所需的促炎 Th1 型免疫。为了揭示 CD200 表达、LIT 后女性免疫背景与妊娠建立之间的关联，我们进行了此项工作。
使用父系外周血白细胞对 37 名女性进行前妊娠同种免疫，如有妊娠则进行额外的同种免疫。通过流式细胞术测定淋巴细胞表型。通过 FlowCytomix™技术估计有丝分裂原刺激的女性外周血细胞产生的细胞因子。
我们已经表明，78.4%（29/37）的女性在前妊娠 LIT 后 12 个月经周期内怀孕。妊娠建立取决于 CD200 表达的强度，在后来未怀孕的女性中给予的 CD200 淋巴细胞上表达明显更高（P<.05）。CD200 的表达与女性外周血细胞产生的 Th1/Th2 细胞因子的比值呈负相关（P<.05），与 LIT 后女性循环调节性 T 细胞的频率呈正相关（P<.05）。ROC 分析表明，CD200 表达强度和 Th1/Th2 比值是前妊娠 LIT 后妊娠建立的显著预测因子（P<.05 和 P<.01）。
同种异体淋巴细胞上的 CD200 表达升高很可能抑制成功胚胎植入所需的促炎 Th1 型免疫。因此，应该应用个性化的 LIT 方法，以避免这种免疫调节对妊娠建立的负面影响。
