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Rejection in heart transplantation strongly correlates with HLA-DR antigen mismatch
S Sheldon1, P S Hasleton, N A Yonan
1North Western Regional Tissue Typing Laboratory, St. Mary's Hospital, Manchester, United Kingdom.
Insights
Prospective HLA-DR matching in heart transplants significantly reduces rejection episodes. Matching at the HLA-DR locus improves graft survival and optimizes the use of donor hearts.
Area of Science:
- Immunology
- Transplantation Medicine
- Cardiology
Background:
- Human Leukocyte Antigen (HLA) incompatibility is a known trigger for immune responses in transplanted organs.
- While HLA matching is standard in kidney transplantation, its role in heart transplantation is less clear.
- Current heart transplant protocols rarely involve prospective HLA matching.
Purpose of the Study:
- To investigate the impact of HLA antigen mismatching on heart transplant rejection.
- To determine if HLA-DR matching influences the incidence of rejection episodes.
- To assess the potential benefit of prospective HLA-DR matching in heart allocation.
Main Methods:
- Analysis of 2569 endomyocardial biopsies (EMBs) from 157 heart transplant recipients.
- Biopsies were graded for rejection using the International Classification (grade 2 and higher indicates rejection).
- Patients were grouped based on the number of HLA-DR mismatches (0, 1, or 2).
Main Results:
- A significantly lower frequency of high-grade rejection (grade ≥2) was observed in patients with zero HLA-DR mismatches (18%) compared to one (29%) or two (34%) mismatches (P < 0.00005).
- No significant effect on rejection rates was found for HLA-A or HLA-B mismatches, except for HLA-B at 3 months post-transplant.
- The close linkage between HLA-B and HLA-DR loci may explain the observed effects.
Conclusions:
- Heart transplants matched at the HLA-DR locus demonstrate a reduced incidence of rejection requiring increased immunosuppression.
- Prospective HLA-DR matching should be considered for donor heart allocation to improve outcomes.
- Implementing HLA-DR matching can lead to more efficient utilization of scarce donor hearts.
Abstract:
It is well established that incompatible HLA antigens presented by donor tissue readily evoke an immune response. Prospective HLA matching policies, widespread in European kidney transplant centers have reduced the level of HLA mismatching and have significantly improved graft survival. The influence of HLA incompatibility in heart transplantation remains controversial, and prospective HLA matching is seldom achieved. We examined the role of HLA antigen mismatching on transplant rejection by analyzing 2569 endomyocardial biopsies (EMB) from 157 consecutive orthotopic heart transplants performed from April 1987 to August 1993 in our own center. Biopsies were graded according to the accepted International Classification, with grade 2 and higher indicating rejection. Among 91 patients who received a 2 HLA-DR mismatch transplant 34% of 1624 biopsies analyzed were graded as > or = 2. This frequency fell to 29% of 797 biopsies for 53 patients with a one-HLA-DR mismatch and to 18% of 148 biopsies for 13 patients in the zero-HLA-DR-mismatch group (P < 0.00005). No significant effect on EMB grade frequencies was observed using the same method of analysis with transplants mismatched at the HLA-A or HLA-B loci apart from analysis of HLA-B matched transplants at 3 months posttransplant (P = 0.02). The close linkage of the HLA-B and HLA-DR loci may account for this observation. The results of this study show that heart transplants matched at the HLA-DR locus have a significantly reduced incidence of EMB grades indicative of rejection requiring augmented immunosuppressive therapy. We propose that prospective HLA-DR matching should be adopted for allocation of donor hearts for more efficient use of this precious and limited resource.