Predictive value of human leucocyte antigen epitope matching using HLAMatchmaker for graft outcomes in a predominantly African‐American renal transplant cohort

Abstract

The HLAMatchmaker program is based on the donor/recipient comparison of the polymorphic triplet amino-acid sequences of the antibody-accessible regions on the human leucocyte antigen (HLA) molecule. The previous reports on its predictive value for renal allograft outcomes are conflicting. We conducted a retrospective study in a predominantly African-American (AA) cohort (N = 101, 94% AA). HLA typing was performed by molecular methods and triplet matching using HLAMatchmaker. Study end points included graft survival and incidence of acute rejection. The relationship between the number of triplet mismatches (TMM) and the degree of HLA antigen MM was evaluated using Pearson's correlation coefficient. Logistic regression models were used to examine the association between triplet matching and the study end points. Kaplan-Meier and Cox proportional hazard models were used for graft survival analysis. The strongest relationship between the number of TMM and HLA antigen MM was observed for HLA-DQ (r = 0.88). The association between triplet matching at HLA-A, -B, -DR and -DRw HLA loci and the study end points was not statistically significant. However, after grouping, the unadjusted estimates of graft survival for those with more than 10 Class I TMM were significantly worse than the others (p = 0.03). Adjusting for the effect of donor source, recipient characteristics and the immunosuppressive regimen did not change this association (hazard ratio = 0.2, confidence interval = 0.04-1.1). We conclude that triplet matching using HLAMatchmaker can provide useful prognostic information in kidney transplantation and that more than 10 donor/recipient Class I HLA TMM is predictive of worse graft outcome.

The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation

“…14 In a small single-center study of 101 kidney transplant recipients with follow-up period of less than 2 years, transplant recipients with greater than 10 class I triplet mismatches experienced an increased risk of grafts loss in excess by 5 times compared to those with 10 or lesser class I triplet mismatches. 15 However, a similar association was not observed between class I eplet HLA mismatches and overall graft loss. 16 These studies were limited by short follow-up period and analysis restricting to predominantly class I mismatches.…”

Predicting the Immunogenicity of Human Leukocyte Antigen Class I Alloantigens Using Structural Epitope Analysis Determined by HLAMatchmaker

“…The HLAMatchmaker algorithm considers each HLA specificity as multiple linear triplet-defined epitopes and performs intraand interlocus comparisons to identify the number of shared and nonshared triplets between donor and recipient. The number of triplet amino-acid mismatches between donor and recipient HLA has been shown to correlate with renal allograft survival (15,16) and the likelihood of HLA alloantibody formation (17,18). However, the linear definition of triplet amino-acids provides an incomplete assessment of conformational epitopes resulting from folding of aminoacid chains in the tertiary HLA molecule.…”

A Structurally Based Approach to Determine HLA Compatibility at the Humoral Immune Level

“…The patient's HLA phenotype represents the repertoire of self-triplets and HLAMatchmaker determines for each mismatched HLA antigen, which triplets in corresponding sequence positions are different. HLAMatchmaker-based matching improves transplant outcome [2][3][4][5][6], and is useful in serum analysis and the identification of acceptable mismatches for alloimmunized kidney transplant candidates [7][8][9][10][11][12][13][14][15][16] and refractory thrombocytopenic patients requiring matched platelet transfusions [17,18] The original version of HLAMatchmaker considers triplets, i.e. linear sequences of three residues at least one of which would be polymorphic [1].…”