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Int. J. Mol. Sci. 2018, 19(9), 2618; https://doi.org/10.3390/ijms19092618

A Valine Mismatch at Position 129 of MICA Is an Independent Predictor of Cytomegalovirus Infection and Acute Kidney Rejection in Simultaneous Pancreas–Kidney Transplantation Recipients

1
Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
2
Post-Graduation Program in Genetics and Molecular Biology, Genetics Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil
3
Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, 44892 Bochum, Germany
*
Author to whom correspondence should be addressed.
Received: 19 August 2018 / Revised: 30 August 2018 / Accepted: 31 August 2018 / Published: 4 September 2018
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Abstract

The polymorphic major histocompatibility complex class I chain-related molecule A (MICA) and its soluble form (sMICA) interact with activating receptor natural-killer group 2 member D (NKG2D) on natural-killer (NK) and T cells, thereby modifying immune responses to transplantation and infectious agents (e.g., cytomegalovirus). Two single-nucleotide polymorphisms (SNPs), rs2596538GA in the MICA promoter and rs1051792AG in the coding region (MICA-129Val/Met), influence MICA expression or binding to NKG2D, with MICA-129Met molecules showing higher receptor affinity. To investigate the impact of these SNPs on the occurrence of cytomegalovirus infection or acute rejection (AR) in individuals who underwent simultaneous pancreas–kidney transplantation (SPKT), 50 recipient-donor pairs were genotyped, and sMICA levels were measured during the first year post-transplantation. Recipients with a Val-mismatch (recipient Met/Met and donor Val/Met or Val/Val) showed shorter cytomegalovirus infection-free and shorter kidney AR-free survival. Additionally, Val mismatch was an independent predictor of cytomegalovirus infection and kidney AR in the first year post-transplantation. Interestingly, sMICA levels were lower in rs2596538AA and MICA129Met/Met-homozygous recipients. These results provide further evidence that genetic variants of MICA influence sMICA levels, and that Val mismatch at position 129 increases cytomegalovirus infection and kidney AR risk during the first year post-SPKT. View Full-Text
Keywords: simultaneous pancreas–kidney transplantation; Val129Met; MICA; cytomegalovirus; acute and latent cytomegalovirus infection; sMICA; dimorphism; genetic predisposition simultaneous pancreas–kidney transplantation; Val129Met; MICA; cytomegalovirus; acute and latent cytomegalovirus infection; sMICA; dimorphism; genetic predisposition
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Michita, R.T.; Chies, J.A.B.; Schramm, S.; Horn, P.A.; Heinemann, F.M.; Wunsch, A.; Viebahn, R.; Schenker, P.; Rebmann, V. A Valine Mismatch at Position 129 of MICA Is an Independent Predictor of Cytomegalovirus Infection and Acute Kidney Rejection in Simultaneous Pancreas–Kidney Transplantation Recipients. Int. J. Mol. Sci. 2018, 19, 2618.

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