KIR Receptors and HLA-C in the maintenance of pregnancy

FLORES AC, MARCOS CY, PALADINO N, ARRUVITO L., WILLIAMS F, MIDDLETON D., FAINBOIM

TISSUE ANTIGENS

WILEY-BLACKWELL PUBLISHING, INC

Año: 2007 vol. 69 p. 112 - 113

0001-2815

Abstract The present study demonstrated that patients who have recurrent spontaneous abortions (RSA) presented a decreased number of killer immunoglobulin-like inhibitory receptors (KIR), in particular KIR2DL2. The KIR AA genotype was found increased in comparison with controls. Individuals AA will also be homozygous for 2DL3, which in contrast to 2DL2, show a weaker interaction with C1 ligands and therefore a weaker inhibition. The present study might support that in RSA patients, the balance between inhibitory and activating receptors present in natural killer cells is inclined toward an activating state that may contribute to pregnancy loss. During the early phase of pregnancy, natural killer (NK) cells constitute the main lymphocytes in the human uterine decidua (1). These cells have been postulated as the protectors of the trophoblast by a mechanism so far not completely elucidated. NK cells possess a repertoire of activating and inhibitory receptors. The killer immunoglobulin- like receptors (KIRs) represent a highly polymorphic system not only by the number of alleles observed in the population but also for the variable number of genes expressed by different individuals. KIRs recognize as ligands on the trophoblast, human leukocyte antigen (HLA)-C, and HLA-G molecules (2). To investigate whether there is an association between KIR receptors and the outcome of pregnancy we compared the KIR gene repertoire of a cohort of 30 fertile couples (without previous abortions) with a panel of 139 healthy controls and with 88 couples suffering from three or more recurrent spontaneous abortions (RSA). Typing of KIR genes by PCR-sequence-specific oligonucleotide probing technique was performed as previously described (3). Two-sided Fisher?s exact test for 2 _ 2 tables was used to compare the KIR genes frequencies between the groups of patients and controls. Odds ratio (OR) with a 95% confidence interval was calculated to evaluate the relative risk in each patient?s group. P values < 0.05 were considered statistically significant, P values < 0.01 very significant, and P values < 0.001 extremely significant. On the basis of gene content, there are two distinct KIR haplotypes, termed A and B. The A haplotype has up to seven KIR loci with only one activating receptor, KIR2DS4. The B haplotypes show the presence of extra loci not present in the A haplotype. These include the inhibitory receptors KIR2DL2 and KIR2DL5 and the activating receptors KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS5, and KIR3DS1 (4). The AA genotype was found present in 29.6% (26/88) of RSA patients vs 17.3% (24/139) of control women (a similar frequency of 17.1% was detected in fertile women); P ¼ 0.03, OR 2.0; F 2 igure 1. We found in RSA patients a decreased frequency of several inhibitory genes. However, only the decreased T A N 7 6 2 _ 8