Evaluation of T cell cytokines and their role in recurrent miscarriage

Abstract

Recurrent miscarriage (RM) is defined as two or more consecutive pregnancy losses that affect approximately 5% of conceived women worldwide. RM is a multi-factorial reproductive problem and has been associated with parental chromosomal abnormalities, embryonic chromosomal rearrangements, uterine anomalies, autoimmune disorders, endocrine dysfunction, thrombophilia, life style factors, and maternal infections. However, the exact cause is still undecided in remaining 50% of cases. Immunological rejection of the embryo due to exacerbated maternal immune reaction against paternal embryonic antigens has been set forth as one of the significant reason for RM. The accurate means that shield the embryo during normal pregnancy from the attack of maternal immune network and dismissal are inadequately implicit. However, it is suggested that the genetically irreconcilable embryo escapes maternal immune rejection due to communication among many vital cytokines exuded at maternal-embryonic interface both by maternal and embryonic cells. Previous investigations suggested the Th1/Th2 dominance in altered immunity of RM patients, according to which the allogenic embryo flees maternal T cell reaction by inclining the Th0 differentiation toward Th2 pathway resulting into diminished pro-inflammatory Th1 immunity. However, recently pro-inflammatory Th17 cells and immunoregulatory Treg cells have been discovered as essential immune players in RM besides Th1/Th2 components. Cytokines are believed to develop a complicated regulatory network so as to establish a state of homeostasis between the semi-allogenic embryo and the maternal immune system. However, an adverse imbalance among cytokines at maternal-embryonic interface perhaps due to their gene polymorphisms may render immunoregulatory means not enough to re-establish homeostasis and thus may collapse pregnancy.

Keywords: Cytokines; Recurrent miscarriage; Th1 immunity; Th17 cells; Th2 immunity; Treg cells.