Cyclosporine A improves pregnancy outcomes in women with recurrent pregnancy loss and elevated Th1/Th2 ratio

J Cell Physiol. 2019 Aug;234(10):19039-19047. doi: 10.1002/jcp.28543. Epub 2019 Mar 28.

Abstract

Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)-dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real-time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme-linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T-bet mRNA expression (p < 0.0001), interferon-γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine-treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome.

Keywords: Th1; Th2; cyclosporine; live birth; recurrent pregnancy loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / drug therapy*
  • Abortion, Habitual / pathology
  • Adult
  • CD4 Lymphocyte Count
  • Cyclosporine / therapeutic use*
  • Female
  • GATA3 Transcription Factor / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / genetics
  • Pregnancy
  • Pregnancy Outcome
  • RNA, Messenger / genetics
  • T-Box Domain Proteins / genetics
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • GATA3 Transcription Factor
  • GATA3 protein, human
  • IFNG protein, human
  • Immunosuppressive Agents
  • RNA, Messenger
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Cyclosporine