HLA class I DNA typing of 215 “HLA‐A, ‐B, ‐DR zero mismatched” kidney transplants

Abstract

DNA typing for HLA class II improves the typing quality and this was shown previously to be relevant for kidney graft survival. In this project we addressed the question whether molecular typing for HLA class I also increases the efficacy of HLA matching in kidney transplantation. 215 HLA-A,-B,-DR zero-mismatched donor/recipient pairs as defined by serological typing were selected. Retrospective HLA-A and HLA-B typing was performed both by the PCR-SSP and the PCR-SSOP method. DNA typing for HLA-A revealed discrepant results to serology in 5.7% of the donors and 2.8% of the recipients. HLA-B typing discrepancies were found in 6.6% of the donors and 5.6% of the recipients. 10.4% of the donors and 6.5% of the recipients showed either an HLA-A or an HLA-B discrepancy Nearly one-third of the HLA-A discrepancies affected A19 splits. The most common reason for HLA-A discrepancies was the erroneous assignment of serological blanks, whereas HLA-B errors were caused mainly by the assignment of incorrect specificities. DNA typing allowed the definition of HLA-A and -B split specificities in all 118 "splitable" cases for which only broad specificities were reported based on serological typing. A total of 183 DNA class I compatible transplants had a 15% higher one-year graft survival rate than 32 transplants for which DNA typing revealed a class I incompatibility

HLA‐AB typing by polymerase‐chain reaction with sequence‐specific primers: more accurate, less errors, and increased resolution compared to serological typing

“…In this study, a high error frequency (34–35%) was also found. Mytilineos et al (5) typed kidney‐transplantation donor‐recipient pairs using PCR‐SSOP and PCR‐SSP. Thirty‐two of 215 pairs considered as HLA‐A, ‐B, ‐DR zero mismatch pairs at the time of transplantation were shown to be A or B incompatible.…”

Re-exposure to Mismatched HLA Class I Is a Significant Risk Factor for Graft Loss: Multivariable Analysis of 259 Kidney Retransplants

“…However, when our analysis was repeated making the assumption that such antigens were not repeat mismatched with the previous donor, the Hazard Ratio estimate associated with HLA-DR remained non-significant at 0.90 (95% CI 0.48 to 1.71, Pϭ0.75). Finally, there has been clear demonstration of incorrect HLA identification using serological methodologies for both class I and class II, with improved survival in even small numbers of patients when matched on the basis of genotyping (27,28). It may be that prospective genotype identification will have an impact on retransplant survival.…”

Fluorotyping of HLA‐DRB by sequence‐specific priming and fluorogenic probing

“…Today, HLA‐DRB typing in clinical practice is nearly exclusively performed by molecular methods. Molecular typing for HLA class II antigens has improved the typing quality and this was shown to be relevant for donor‐recipient matching in organ transplantation ( 10, 11). Due to its high reliability and simple interpretation, PCR‐SSP has been shown so far to be the most successful technique for HLA‐typing among the standard PCR‐based methods.…”