Maternal KIR Repertoire and KIR/HLA-C Recognition Model in Early Pregnancy and Implantation Failure

Abstract

In the frame of EMBIC study, maternal KIR and trophoblastic HLA-C matching was estimated in 39 randomly selected cases of women who were undergoing vacuum uterine curettage for therapeutic termination of first trimester missed pregnancy (Group A = 19) or elective termination of normal pregnancy (Group C = 20). DNA from decidual cells was used for maternal KIR genotyping by Luminex, while DNA from trophoblastic cells was used for foetal HLA C typing by PCR-SSP. HLA-C alleles were grouped as C1 and C2. According to the results, the women in group A were found to possess fewer inhibitory KIR genes than the women in group C (31.6% of A women had all 3 inhKIR -2DL1, 2DL2, 2DL3- receptors vs. 80% of the Controls), while no differences were found in the number of actKIR genes detected in the two groups. The inhKIR2DL1 was statistically significant decreased in group A compared to the controls (p = 0.0043). The percentage of cases possessing the KIR2DL1-C2 combination, which is associated with increased inhibition, was found to be lower in group A in comparison to group C, while the combination KIR2DL3-C1, which is associated with increased activation, was found in higher percentage in group A than in controls. Our findings support the suggestion that uNK cells of women predisposed to miscarriage may have a higher activating potential and that both inhibitory and activating KIR receptors on uNK cells are important for the maintenance of pregnancy.