Survival of DNA HLA-DR typed and matched cadaver kidney transplants. The Collaborative Transplant Study

Area of Science:

• Immunogenetics
• Transplantation immunology
• Molecular diagnostics

Background:

• Serological human leukocyte antigen (HLA) matching for cadaver kidney transplants shows uncertain clinical value, with lower success rates than sibling grafts.
• Discrepancies exist between serological and DNA-based HLA typing, particularly for HLA-DR, potentially affecting transplant outcomes.
• Previous studies suggest up to 25% of serological HLA-DR typings may be inaccurate compared to DNA-RFLP methods.

Purpose of the Study:

• To investigate if inaccurate serological HLA-DR typing contributes to the lower-than-expected success rates of HLA-matched cadaver kidney transplants.
• To compare the accuracy of serological HLA typing with DNA-RFLP methods in a large-scale cadaveric kidney transplant study.
• To determine the impact of HLA-DR mismatches, identified by DNA typing, on one-year kidney transplant success rates.

Main Methods:

• Multi-center study involving 58 transplant centers and over 4000 frozen tissue samples.
• Blind HLA-DR typing using DNA-RFLP method performed at a central study laboratory.
• Comparison of DNA-based typing results with serological typing data reported by individual transplant laboratories.

Main Results:

• Significant HLA-DR mismatches were identified in transplants reported as serologically matched: 27% of HLA A, B, DR compatible and 28% of HLA B, DR compatible transplants.
• One-year success rate for DNA-matched HLA A, B, DR grafts was 87%, compared to 69% for mismatched grafts (p<0.02).
• One-year success rate for DNA-matched HLA B, DR grafts was 85%, compared to 72% for mismatched grafts (p<0.01).

Conclusions:

• A substantial number of kidney transplants previously considered HLA matched are, in fact, mismatched at the HLA-DR locus based on accurate DNA typing.
• These previously unrecognized HLA-DR mismatches likely account for unexplained graft failures and lower-than-expected success rates in cadaveric kidney transplantation.
• Implementing accurate DNA-based HLA typing is crucial for improving the clinical management and outcomes of kidney transplantation.