Altered T‐cell subpopulations in recurrent pregnancy loss patients with cellular immune abnormalities

• Published in: Journal of cellular physiology Vol. 234; no. 4; pp. 4924 - 4933
• Main Authors: Abdolmohammadi Vahid, Samaneh, Ghaebi, Mahnaz, Ahmadi, Majid, Nouri, Mohammad, Danaei, Shahla, Aghebati‐Maleki, Leili, Mousavi Ardehaie, Reza, Yousefi, Bahman, Hakimi, Parvin, Hojjat‐Farsangi, Mohammad, Rikhtegar, Reza, Yousefi, Mehdi
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2019
• Subjects: Abnormalities; Abortion, Habitual - genetics; Abortion, Habitual - immunology; Adult; Biomarkers; Deregulation; exhausted regulatory T cell; exhausted T cell; Female; Flow cytometry; GATA-3 protein; GATA3 Transcription Factor - metabolism; Gene expression; Glucocorticoid-Induced TNFR-Related Protein - metabolism; Helper cells; Humans; Immune system; Interferon regulatory factor 4; Interferon Regulatory Factors - metabolism; Lymphocytes; Lymphocytes T; microRNA; MicroRNAs - genetics; miRNA; Miscarriage; Patients; Polymerase chain reaction; Pregnancy; recurrent pregnancy loss; regulatory T cell; Ribonucleic acid; RNA; Subpopulations; T helper 17; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Transcription factors; Young Adult; exhausted regulatory T cell; microRNA; exhausted T cell; T helper 17; regulatory T cell; recurrent pregnancy loss
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.27290

Recurrent pregnancy loss (RPL) is a multifactorial disorder of women in reproductive age, which in some cases is caused by immunologic abnormalities. In this study, we aimed to evaluate cellular and molecular components of the immune system like different T‐cell subsets and their regulating microRNAs (miRNAs) in RPL women and control group. Fifty RPL and 50 healthy subjects were recruited. Subsets of T cells, including regulatory T (Treg) cells, helper T (Th) 17 cells, exhausted T cells, exhausted Treg cells were evaluated by flow cytometry. Transcription factors of T cells and related miRNA profile were quantified using real‐time polymerase chain reaction (RT‐PCR). Assessment showed that Treg and exhausted T cells, were decreased in RPL patients (p = 0.009 and 0.02, respectively), while an increase was observed in Th17 and exhausted Treg frequency ( p = 0.013 and 0.0037, respectively). Messenger RNA expression level of T‐bet and IRF4 was upregulated in RPL patients ( p = 0.011 and 0.0001, respectively), while Th2‐ and Treg‐related transcription factors, GATA3 and GITR, were downregulated in these patients compared with the healthy subjects ( p = 0.0008 and <0.000, respectively). Treg‐associated miRNAs, the miR‐106b‐25–93 cluster, showed a higher rate in RPL patients ( P = 0.007, 0.001, and 0.029, respectively), however, we observed no significant difference in the expression level of Th17‐associated miRNA, mir‐326. According to the results, we concluded that unbalanced immune responses and deregulated function of T‐cell subsets may lead to reproduction‐related failure like a miscarriage. Therefore, evaluation of immune cells and related miRNA profile may serve as prognostic biomarker for the treatment of RPL patients. Balanced immune responses are required for a successful pregnancy therefore lack of suppressor mechanisms and increased inflammatory parameters may negatively affect the pregnancy.