Characterization of the novel HLA-B*55:122 allele by two next-generation sequencing methods.

The novel HLA-B*55:122 allele was characterized using two next generation sequencing technologies.

MICA Mutant A5.1 Influences BK Polyomavirus Reactivation and Associated Nephropathy After Kidney Transplantation.

BACKGROUND: BK polyomavirus (BKPyV) frequently reactivates in kidney transplant recipients during immunosuppressive therapy and triggers BKPyV-associated nephropathy and graft rejection. Determining effective risk factors for BKPyV reactivation is required to achieve efficient prevention. METHODS: This study investigated the role of major histocompatibility complex (MHC) class I-related chain A (MICA) in BKPyV reactivation in a cohort of 144 transplant donor/recipient pairs, including recipients with no reactivation (controllers) and those with mild (virurics) or severe (viremics) BKPyV reactivation after graft receipt. RESULTS: We show that, in the kidney, MICA is predominantly expressed in tubule epithelial cells, the natural targets of BKPyV, questioning a role for MICA in the immune control of BKPyV infection. Focusing on MICA genotype, we found a lower incidence of BKPyV reactivation in recipients of a renal graft from a donor carrying the MICA A5.1 mutant, which encodes a truncated nonconventional MICA. We established that a mismatch for MICA A5.1 between transplant donor and recipient is critical for BKPyV reactivation and BKPyV-associated nephropathy. Functionally, we found that a low prevalence of BKPyV reactivation was associated with elevated anti-MICA sensitization and reduced plasma level of soluble MICA in recipients, 2 potential effector mechanisms. DISCUSSIONS: These findings identify the MHC-related MICA as an immunogenetic factor that may functionally influence anti-BKPyV immune responses and infection outcomes.

Relevance of KIR gene polymorphisms in bone marrow transplantation outcome.

Natural Killer (NK) cells may be involved both in allogeneic bone marrow transplantation (BMT) rejection and graft-versus-host disease (GVHD). The physiologic functions of NK cells appear to be regulated by diverse non-inhibitory and inhibitory receptors including the killer cell immunoglobulin-like receptors (KIR). Although human leukocyte antigen (HLA) epitope mismatches are well-known causes of NK alloreactivity, the role of KIR genes in transplantation remains to be further investigated. In this study, we have evaluated whether KIR genotype differences between donors and recipients of HLA identical (related and unrelated) compared with HLA non-identical unrelated BMT, had an impact on transplantation outcome. Our results show that 5 of 15 KIR genes were always identical in donors and recipients and most variations were observed in the number and specificity of noninhibitory KIR genes. Based on the presence or absence of particular KIR genes, 70 different genotypes were obtained from all individuals. According to the donor or recipient KIR genotype, different combination patterns were described. Interestingly, when the recipient KIR genotype was "included" in the donor KIR genotype, 100% (11/11 pairs) of unrelated BMT developed GVHD compared with 60% (18/30) in all other combinations (p = 0.012). In contrast, no GVHD was observed in related BMT when the recipient KIR genotype was "included" in the donor KIR genotype (p = 0.0001). In conclusion, our results reveal a great diversity for KIR genotypes in donors and recipients of BMT and that the risk of GVHD was maximum in unrelated BMT when the recipient KIR genotype was "included" in the donor KIR genotype.