Abstract

BackgroundThe published results regarding lymphocytes immunotherapy for unexplained recurrent miscarriage (uRM) patients are conflicting due to different screening criteria and therapeutic protocols. The objective of the present study is to evaluate the effectiveness of immunotherapy using low-dose lymphocytes in patients with uRM and Th1/Th2/Treg paradigm disorders.MethodsSixty-four uRM patients who received low-dose lymphocytes immunotherapy served as the immunotherapy group, while the other 35 women who did not receive the treatment served as the control group. The proportions of peripheral blood Th1 cells, Th2 cells and Treg cells; and the concentration of TGF-β1 in serum were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively, before and after the immunotherapy.ResultsThe proportion of Th1 cells was significantly decreased while the proportions of Th2 cells and Treg cells were significantly increased in immunotherapy group patients after treatment. In addition, the concentration of TGF-β1 in serum was significantly higher after immunotherapy than before. Forty-three uRM patients achieved pregnancy after receiving immunotherapy and 5 patients underwent miscarriages in the immunotherapy group (11.6%, 5/43), while 8 of the 23 pregnant patients experienced a miscarriage in the control group (34.8%, 8/23; p < 0.05).ConclusionsLow-dose lymphocyte immunotherapy is beneficial for restoring balance in the Th1/Th2/Treg paradigm and improving pregnancy outcome in uRM patients.Trial registrationNCT03081325. ClinicalTrials.gov. Retrospectively registered July 2015.

Highlights

  • The published results regarding lymphocytes immunotherapy for unexplained recurrent miscarriage patients are conflicting due to different screening criteria and therapeutic protocols

  • The proportion of abnormal T helper 1 cells (Th1) cells in unexplained recurrent miscarriage (uRM) patients was significantly decreased after immunotherapy (37.69 ± 5.33% vs. 35.83 ± 6.86%, respectively; n = 33, P = 0.038; Fig. 1a and Table 2)

  • The proportion of abnormal T helper 2 cells (Th2) cells was significantly increased after immunotherapy

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Summary

Introduction

The published results regarding lymphocytes immunotherapy for unexplained recurrent miscarriage (uRM) patients are conflicting due to different screening criteria and therapeutic protocols. 1–5% of all couples of reproductive age suffer from recurrent miscarriage (RM) [1]. This condition can lead to serious problems for patients’ health, spousal relationships, and quality of life. The etiology of RM is often unclear and may be multifactorial, with controversial diagnoses and treatment. The mother accepts the fetus and maintains its development as an allograft that benefits from maternal-fetal immune tolerance. It has been reported in previous studies that the homeostasis of Th1/Th2 cytokines regulates maternal-fetal immune tolerance during pregnancy [4, 5].

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