Endometriosis is a disease in which endometriotic tissue occurs outside the uterus. Its pathogenesis is still unknown. The most widespread hypothesis claims that ectopic endometrium appears as a result of retrograde menstruation and its insufficient elimination by immunocytes. Some reports have shown expression of non-classical HLA-G molecules on ectopic endometrium. HLA-G is recognized by KIR2DL4, LILRB1 and LILRB2 receptors on natural killer (NK) and other cells. These receptors are polymorphic, which may affect their activity. In this study we investigated whether HLA-G, KIR2DL4, LILRB1 and LILRB2 polymorphisms may influence susceptibility to endometriosis and disease progression. We used polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and allelic discrimination methods with TaqMan SNP Genotyping Assays for typing of 276 patients with endometriosis and 314 healthy fertile women. The HLA-G rs1632947:GG genotype was associated with protection against the disease and its severe stages; HLA-G rs1233334:CT protected against progression; LILRB1 rs41308748:AA and LILRB2 rs383369:AG predisposed to the disease and its progression. No effect of KIR2DL4 polymorphism was observed. These results support the role of polymorphisms of HLA-G and its receptors LILRB1 and LILRB2 in susceptibility to endometriosis and its progression.

The KIR2DL4 receptor and its ligand HLA-G are considered important for fetal-maternal immune tolerance and successful pregnancy. The absence of a particular variant of KIR2DL4 might be a bad prognostic factor for pregnancy outcome. However, it could be compensated by the presence of the respective LILRB1 allele. Therefore, we investigated the KIR2DL4, LILRB1 and HLA-G polymorphisms in 277 couples with spontaneous abortion and 219 control couples by HRM, PCR-SSP and RFLP methods. We found a protective effect of women’s heterozygosity in −716 HLA-G (p = 0.0206) and LILRB1 (p = 0.0131) against spontaneous abortion. Surprisingly, we observed more 9A/10A genotypes of KIR2DL4 gene carriers in the group of male partners from the miscarriage group in comparison to the men from the control group (p = 0.0288). Furthermore, there was no association of women’s KIR2DL4 polymorphism with susceptibility to spontaneous abortion. Multivariate analysis indicated that women’s −716 HLA-G and LILRB1 and men’s KIR2DL4 9A/10A are important in terms of the protection or susceptibility to miscarriage, respectively (p = 0.00968). In conclusion, a woman’s heterozygosity in HLA-G and LILRB1 might be an advantage for a success of reproduction, but the partner’s heterozygosity in 9A/10A KIR2DL4 alleles might not.

Recipient NK cells may detect the lack of recipient's (i.e., self) HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs). KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft. We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del. Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.