Intravenous immunoglobulin G modulates peripheral blood Th17 and Foxp3(+) regulatory T cells in pregnant women with recurrent pregnancy loss

Am J Reprod Immunol. 2014 May;71(5):441-50. doi: 10.1111/aji.12208. Epub 2014 Mar 19.

Abstract

Problem: Th17 cells and Foxp3(+) regulatory T (Treg) cells have been proposed as new risk factors for recurrent pregnancy loss (RPL). Intravenous immunoglobulin G (IVIG) was reported to modulate various immune cells. In this study, we investigated the effect of IVIG on the levels of Th17 and Treg cells and pregnancy outcome in women with RPL.

Method of study: Thirty-seven pregnant women with RPL were enrolled in this study. All had cellular immune abnormality in preconceptional evaluation. Blood was drawn on the day of IVIG treatment and 1 week later from the study subjects during early pregnancy. The proportions of IL-17(+) and Foxp3(+) T cells were analyzed using flow cytometry.

Results: Study population was divided into four groups (Q1-Q4) based on ascending order of the levels of Th17 and Foxp3(+) T cells. IVIG down-regulated Th17 cells in the highest quartile, Q4 (P = 0.001), and up-regulated CD4(+) Foxp3(+) T cells in Q1 and Q2 (P = 0.025 and 0.029, respectively). In addition, Th17/CD4(+) Foxp3(+) T cell ratio decreased in Q4 (P = 0.040). We also found a positive trend between successful pregnancy outcome and CD8(+) IL-17(+) T cells before IVIG treatment (P = 0.05).

Conclusion: Intravenous immunoglobulin G treatment modulated imbalance of Th17 and Foxp3(+) Treg cells in pregnant RPL women with cellular immune abnormality.

Keywords: IL-17; Th17 cells; intravenous immunoglobulin; recurrent pregnancy loss; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / drug therapy*
  • Abortion, Habitual / immunology
  • Abortion, Habitual / pathology
  • Adult
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Drug Administration Schedule
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Gene Expression
  • Humans
  • Immunity, Cellular
  • Immunoglobulin G / blood
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Interleukin-17 / biosynthesis
  • Pregnancy
  • Pregnancy Outcome
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / pathology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Interleukin-17