title: The Synergistic Effect of Class II HLA Epitope-Mismatch and Nonadherence on Acute Rejection and Graft Survival.
abstract: Predicting long-term outcomes in renal transplant recipients is essential to optimize medical therapy and determine the frequency of posttransplant histologic and serologic monitoring. Nonadherence and human leukocyte antigen (HLA) mismatch are risk factors that have been associated with poor long-term outcomes and may help individualize care. In the present study, class II HLA mismatches were determined at the HLA epitope level in 195 renal transplant recipients in whom medication adherence was prospectively measured using electronic monitors in medication vial caps. Recipients were grouped by medication adherence and high (≥10 HLA-DR, ≥17 HLA-DQ) or low epitope-mismatch load. We found that the combination of higher epitope mismatch and poor adherence acted synergistically to determine the risk of rejection or graft loss. Nonadherent recipients with HLA-DR epitope mismatch ≥10 had increased graft loss (35% vs. 8%, p < 0.01) compared to adherent recipients with low epitope mismatch. At the HLA-DQ locus nonadherent recipients with HLA-DQ epitope mismatch ≥17 had increased graft loss (33% vs. 10%, p < 0.01) compared to adherent recipients with low epitope mismatch. Subclinical nonadherence early posttransplant combined with HLA class II epitope mismatch may help identify recipients that could benefit from increased clinical, histologic, and serologic monitoring.
authors.affiliation: Department of Medicine, University of Manitoba, Diagnostic Services of Manitoba, Manitoba, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Wiebe
authors.affiliation: Department of Pediatrics, University of Minnesota, MN.
authors.forename: T E
authors.initials: TE
authors.lastname: Nevins
authors.affiliation: Departments of Medicine and Pediatrics, University of Minnesota, MN.
authors.forename: W N
authors.initials: WN
authors.lastname: Robiner
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, MN.
authors.forename: W
authors.initials: W
authors.lastname: Thomas
authors.affiliation: Department of Surgery, University of Minnesota, MN.
authors.forename: A J
authors.initials: AJ
authors.lastname: Matas
authors.affiliation: Departments of Medicine and Immunology, University of Manitoba, Diagnostic Services of Manitoba, Manitoba, Canada.
authors.forename: P W
authors.initials: PW
authors.lastname: Nickerson
mesh_terms: D000328:Adult; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents
keywords: graft survival; immunogenetics; kidney transplantation: living donor; rejection: acute; risk assessment/risk stratification