MICA gene polymorphism in kidney allografts and possible impact of functionally relevant variants

Abstract

It is likely that the polymorphic MICA (MHC class I related chain A) molecules on graft endothelial cells (ECs) may be a target for specific antibodies and T cells directed against solid organ grafts. Although there is evidence for a role of MICA in vascular and transplant biology, genotyping is not performed routinely, and thus there are few correlations between polymorphism and endothelial phenotype. The present study examined the frequency of the various alleles for the nonclassical MHCI MICA gene among a cohort of kidney transplant donors, particularly MICA genetic variants (MICA A5.1 and MICA-129) that may affect MICA expression and function on graft EC. Genotyping was performed on genomic DNA derived from primary cultures of EC established from transplant donors at the time of transplantation. Herein we have reported that among 106 alleles analyzed, 28/69 MICA alleles were distributed among 7 major variants (*00804, *00801, *004, *00201, *00901*, *011, *010), representing 70% of the donors. MICA*008 the most abundant allele (31.1%) was associated with the MICA A5.1 mutation. The majority of donors (52.8%) had at least one MICA A5.l allele, with 13.2% homozygous for this mutation. The MICA-129 val/val genotype, which encodes a low-affinity ligand, was predominant (49%), while the MICA-129 met/met, corresponding to a high-affinity ligand, was observed in 11.3% of the transplants. Our findings highlighted the MICA gene polymorphism that produces functional diversity in transplant recipients with variable interactions between MICA and its receptor NKG2D.