Eplet Mismatch Load Research Articles

HLA-Epitope Matching or Eplet Risk Stratification: The Devil Is in the Details.

“Epitope matching” became a trending topic in organ transplantation. In fact, discussions on clinical implementation and utilization of this approach in organ allocation algorithms are currently on-going. More recently, the term “eplet mismatch load” was introduced in publications. While the terms are often used synonymously, they are NOT equivalent. This short overview is meant to emphasize the differences between the terms epitope matching and eplet mismatching (or mismatch load) as well as to provide perspective on different approaches for interpretation of immune compatibility between the donor of an organ transplant and the recipient. It highlights some of the less explored qualities of HLA-epitopes, and stresses the need to understand the differences between donor and recipient in terms of immunogenicity and ability to initiate an immune response. While the field of “epitope matching” shows enormous promise, it is still in its infancy. What is sorely missing is understanding of EPITOPE COMPATIBILITY rather than matching. Further work is required before new approaches can be introduced into routine clinical practice and organ allocation schemes.

Correlation and agreement between eplet mismatches calculated using serological, low-intermediate and high resolution molecular human leukocyte antigen typing methods.

Structural human leukocyte antigen (HLA) matching at the eplet level can be identified by HLAMatchmaker, which requires the entry of four-digit alleles. The aim of this study was to evaluate the agreement between eplet mismatches calculated by serological and two-digit typing methods compared to high-resolution four-digit typing. In a cohort of 264 donor/recipient pairs, the evaluation of measurement error was assessed using intra-class correlation to confirm the absolute agreement between the number of eplet mismatches at class I (HLA-A, -B, C) and II loci (HLA-DQ and -DR) calculated using serological or two-digit molecular typing compared to four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches between the HLA typing methods was also determined. Intra-class correlation coefficients between serological and four-digit molecular typing methods were 0.969 (95% confidence intervals [95% CI] 0.960–0.975) and 0.926 (95% CI 0.899–0.944), respectively; and 0.995 (95% CI 0.994–0.996) and 0.993 (95% CI 0.991–0.995), respectively between two-digit and four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches at class I and II loci was 4% and 16% for serological versus four-digit molecular typing methods, and 0% and 2% for two-digit versus four-digit molecular typing methods, respectively. In this small predominantly Caucasian population, compared with serology, there is a high level of agreement in the number of eplet mismatches calculated using two-compared to four-digit molecular HLA-typing methods, suggesting that two-digit typing may be sufficient in determining eplet mismatch load in kidney transplantation.

Human leukocyte antigen, allele, and eplet mismatches in liver transplantation; observations from a small, single center cohort

BackgroundThe impact of human leukocyte antigen (HLA) matching on outcomes in liver transplantation is controversial. Varying levels of HLA matching resolutions were examined in a uniform patient population with no pre-transplant DSA from a small, single center cohort. MethodsRetrospective chart review from a single center yielded 131 patients, 67 of which were confirmed to be DSA negative, all of which received induction immunotherapy and post-operative immunosuppression. HLA typing was achieved by sequence specific oligonucleotide probe (SSOP) method using LABType® kits. Eplet mismatch analysis was conducted using HLAMatchMaker software. ResultsThe mean number of HLA-A antigen mismatches was significantly higher in patients experiencing acute rejection (1.8 vs 1.6, p = 0.006). Rejection patients more frequently possessed two HLA-A mismatches compared to their non-rejection counterparts (77% vs 43%, p = 0.071). Patient survival was found to be non-significantly decreased in patients with a higher eplet mismatch load at the HLA-A locus (p = 0.155). No other loci were found to be predictive. ConclusionIn conclusion, HLA mismatches were found to increase acute rejection and be associated with decreased patient survival. The outcomes of this study suggest an involvement of HLA-A locus mismatches in predicting liver transplant rejection and patient survival.

Optimizing Outcomes in Pediatric Renal Transplantation Through the Australian Paired Kidney Exchange Program.

Kidney paired donation (KPD) programs offer the opportunity to enable living kidney donation when immunological and other barriers prevent safe directed donation. Children are likely to require multiple transplants during their lifetime; therefore, high-level histocompatibility and organ quality matching are key priorities. Details are given for a cohort of seven pediatric renal transplantations performed through the Australian Kidney Exchange (AKX), including barriers to alternative transplantation and outcomes after KPD. Reasons for entering the KPD program were preformed donor-specific antibodies to their registered donor in five cases, ABO mismatch, and avoidance of the risk of exposure to hepatitis B virus. Four recipients were highly sensitized. All patients received transplants with organs of lower immunological risk compared with their registered donors. HLA eplet mismatch scores were calculated for donor-recipient pairs; three patients had improved eplet mismatch load with AKX donor compared with their registered donor. All grafts are functioning, with a mean estimated glomerular filtration rate of 77 mL/min/1.73 m2 (range 46-94 mL) and a follow-up range of 8-54 months, and no patient experienced clinical or histological rejection. KPD is a viable strategy to overcome many barriers to living donation for pediatric patients who have an otherwise suitable donor and provides an opportunity to minimize immunological risks.