Influence of activating and inhibitory killer immunoglobulin-like receptors on predisposition to recurrent miscarriages

Understanding of the immune events and mechanisms occurring at the feto-maternal interface is likely to help in understanding the ability of the fetus to survive within the maternal body. Evidence supporting extensive roles of natural killer cells during pregnancy gives rise to a possibility that these NK cells can be mis-regulated and involved in fetal allograft rejection. Killer immunoglobulin-like receptors (KIR) play an important role in regulating the NK cell activity through their activating and inhibiting isoforms. Since there exists a considerable, genetically determined variation in the repertoire of KIR receptors between different individuals, a particular maternal KIR repertoire may predispose to recurrent miscarriages (RMs). Gene-specific PCR amplification (PCR-SSP) was used to determine the individual KIR genotypes in women experiencing RM and controls. A higher prevalence of activating KIR genes was seen in patients than in controls. Among women experiencing RM, the BB genotypes were more prevalent (P < 0.0001, OR = 4.4, 95% CI = 2.89-6.69) compared with controls. Our results indicate that the balance between inhibitory and activating receptor-mediated signals present in natural killer cells is inclined toward a more activating state that may contribute to pregnancy loss.