COMPATIBILITY OF HLA-C KIR LIGANDS AND UNEXPLAINED EARLY PREGNANCY LOSS.

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COMPATIBILITY OF HLA-C KIR LIGANDS AND UNEXPLAINED EARLY PREGNANCY LOSS.
Lei Zhang Ph.D , Jueqin Yang , Fangjuan Yao , Lingdi Xu and Lian Fan M.D . ¹ Immunogenetics Laboratory, Shanghai Second Medical University;Shanghai Institute of Immunology, Shanghai, China .

In pregnancy, the placental extravillous trophoblast has a genetic contribution from the father and is thus an allogeneic normal cell in the mother. The only known polymorphic HLA antigens on the fetal trophoblast are HLA-C molecules. HLA-C molecules are ligands for KIR receptors on uNK cells . For these reasons, we detected the HLA-C allele genotyping both in the mother and the fetus, as well as the KIR genotypes and haplotypes in the mother, and analyzed how meternal KIR2Dx and fetal HLA-C genes combine to influence the pregnancy outcome. The results are: 1.The gene frequency of activating KIR2DS2 is significantly increased in unexplained early abortion group compare with control ( 0.11 vs 0.65, P=0.0019). 2. The frequency of the maternal KIR AA genotype is decreased in abortion group ( 37.5% vs 65.0%). In contrast, the frequency of the maternal KIR B genotype is incresed in abortion group (62.5% vs 35.0%), so the ratio of KIR B/A is signifcantly increased in abortion group (1.67 va 0.54). 3. The frequencies of HLA-C group and alleles are similar in abortion and controls. 4. The ratio of inhibitory KIR2DL versus ativating KIR2DS both specific for HLA-C1 and HLA-C2 dramatically decteased in early abortion group. Our results suggest that certain distinct combination of the KIR2D/HLA-C system, particular the paired KIR 2DS2/HLA-C1 are unfavorable for embryo implantation.