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

• Published in: International journal of molecular sciences 2018-09, Vol.19 (9), p.2618
• Main Authors: Michita, Rafael Tomoya, Chies, José Artur Bogo, Schramm, Sabine, Horn, Peter A, Heinemann, Falko M, Wunsch, Andreas, Viebahn, Richard, Schenker, Peter, Rebmann, Vera
• Format: Article
• Language: English
• Subjects: acute and latent cytomegalovirus infection; Adult; Amino Acid Substitution; Antigens; Cytomegalovirus; Cytomegalovirus Infections - genetics; Cytomegalovirus Infections - metabolism; dimorphism; Female; Genetic diversity; genetic predisposition; Graft rejection; Graft Rejection - genetics; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Humans; Infections; Ischemia; Kidney Transplantation; Kidney transplants; Kidneys; Leukemia; Ligands; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Male; MICA; Middle Aged; NK Cell Lectin-Like Receptor Subfamily K - metabolism; Pancreas; Pancreas Transplantation; Prognosis; Proteins; Rejection; simultaneous pancreas–kidney transplantation; Single-nucleotide polymorphism; sMICA; Tissue Donors; Transplantation; Transplants & implants; Val129Met; Valine; Valine - genetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092618

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 promoter and rs1051792AG in the coding region ( -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 influence sMICA levels, and that Val mismatch at position 129 increases cytomegalovirus infection and kidney AR risk during the first year post-SPKT.