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The interaction of major histocompatibility complex class I chain-related protein A (MICA) and its cognate activating receptor natural killer (NK) group 2 member D (NKG2D) receptor plays a significant role in viral immune control. In the context of kidney transplantation (KTx), cytomegalovirus (CMV) frequently causes severe complications. Hypothesizing that functional polymorphisms of the MICA/NKG2D axis might affect antiviral NK and T cell responses to CMV, we explored the association of the MICA-129 Met/Val single nucleotide polymorphism (SNP) (affecting the binding affinity of MICA with the NKG2D receptor), the MICA rs2596538 G/A SNP (influencing MICA transcription), and the NKG2D rs1049174 G/C SNP (determining the cytotoxic potential of effector cells) with the clinical outcome of CMV during the first year after KTx in a cohort of 181 kidney donor-recipients pairs. Univariate analyses identified the donor MICA rs2596538 G allele status as a protective prognostic determinant for CMV disease. In addition to the well-known prognostic factors CMV high-risk sero-status of patients and the application of lymphocyte-depleting drugs, the donor MICA rs2596538 G allele carrier status was confirmed by multivariate analyses as novel-independent factor predicting the development of CMV infection/disease during the first year after KTx. The results of our study emphasize the clinical importance of the MICA/NKG2D axis in CMV control in KTx and point out that the potential MICA transcription in the donor allograft is of clinically relevant importance for CMV immune control in this allogeneic situation. Furthermore, they provide substantial evidence that the donor MICA rs2596538 G allele carrier status is a promising genetic marker predicting CMV viremia after KTx. Thus, in the kidney transplant setting, donor MICA rs2596538 G may help to allow the future development of personal CMV approaches within a genetically predisposed patient cohort.

frontiers in immunology

The Donor Major Histocompatibility Complex Class I Chain-Related Molecule A Allele rs2596538 G Predicts Cytomegalovirus Viremia in Kidney Transplant Recipients