Regulatory T cells improve pregnancy rate in RIF patients after additional IVIG treatment

Abstract

ABSTRACTRIF (repeated implantation failure) women with immunologic basis and cellular abnormalities may benefit from intravenous immunoglobulins (IVIG) as an immunomodulator based on different studies. In this study, we evaluated the effect of IVIG on the frequency and function of Th17 and Treg cells, as two important subgroups of CD4+ T cells in implantation and pregnancy rates. Seventy-two RIF patients with preconception Th1⁄Th2 ratio and natural killer (NK) cells frequency and activity elevation were selected and divided into two groups; 40 out of 72 received IVIG, aspirin, and heparin (anoxaparin) and constituted the treatment group and 32 patients received aspirin and heparin (anoxaparin) and no IVIG and were the control group. Th17, Treg frequency, transcription factors, cytokine gene expression, and cytokine secretion were evaluated by flow cytometry, real-time PCR, and ELISA, respectively. Post-treatment evaluation of the IVIG grouprevealed a significant increase in Treg associated parameters such as Treg frequency (p = 0.0186), Foxp3 (p = 0.0004), and cytokine mRNA levels (IL-10, p = 0.0058 and TGF- β, p = 0.0038), however, in the case of Th17, a significant difference was only observed in a reduction in the RORγt mRNA level (p = 0.0218). In conclusion, IVIG therapy may be a good choice in the treatment of implantation failure in RIF women especially with an immunologic basis, and may improve the implantation and pregnancy rate by affecting immunoregulatory mechanisms such as Tregs.Abbreviations: RIF: repeated implantation failure; IVIG: intravenous immunoglobulin; Th17: T helper 17; Treg: T regulatory; NK cells: natural killer cells; PCR: polymerase chain reaction; ELISA: enzyme-linked immunosorbent assay; RORγt: RAR-related orphan receptor gamma; Foxp3: forkhead box protein P3; IL-17: interleukin-17; LMWH: low-molecular weight heparin; dNK: decidual NK cells