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HLA-A incompatibility associated with enhanced long-term renal graft survival in HLA-B, DR mismatched transplants
D Bućin1, H Ekberg, A Lindholm
1Blood Center, University Hospital, Lund, Sweden.
Insights
HLA-A mismatching improves long-term kidney transplant survival in cyclosporine (CyA)-treated patients, particularly when HLA-B,DR is also mismatched. This finding may enhance graft survival rates and indicate tolerance-promoting markers.
Area of Science:
- Immunogenetics
- Transplantation immunology
- Nephrology
Background:
- Kidney graft survival is crucial for patients with end-stage renal disease.
- Human Leukocyte Antigen (HLA) matching influences transplant outcomes.
- The role of specific HLA loci, like HLA-A, in long-term graft survival requires further elucidation.
Purpose of the Study:
- To analyze the effect of HLA-A matching on long-term cadaver kidney graft survival.
- To investigate the association between HLA-A mismatching and graft survival in cyclosporine-treated patients.
- To determine if the effect of HLA-A matching varies based on HLA-B,DR compatibility.
Main Methods:
- Retrospective analysis of 1085 cyclosporine (CyA)-treated patients.
- Univariate and multivariate analyses to assess HLA-A matching effects.
- Evaluation of graft survival at an average of 6 years post-transplantation.
Main Results:
- HLA-A mismatching was associated with significantly enhanced long-term graft survival (P < 0.05).
- This benefit was most pronounced in HLA-B,DR mismatched transplants and in patients without acute rejection.
- High graft survival rates (78% and 66%) were observed with one or two HLA-A mismatches versus 55% with HLA-A compatibility (P = 0.001).
Conclusions:
- HLA-A mismatching enhances long-term renal graft survival in CyA-treated recipients, especially in HLA-B,DR mismatched transplants.
- These findings could potentially prolong graft survival and suggest tolerance-promoting allogeneic markers in the HLA-A region.
Abstract:
The effect of HLA-A matching on long-term cadaver kidney graft survival was analysed, on average, 6 years after transplantation in a total of 1085 cyclosporine (CyA)-treated patients. A beneficial effect of HLA-A mismatching on graft survival was found by univariate and multivariate analyses (P < 0.05). Enhanced graft survival was associated with HLA-A mismatching in transplants mismatched for HLA-B,DR (P = 0.03), but not in HLA-B,DR compatible transplants. High 6 year graft survival rates, 78% and 66%, were found in transplants mismatched for two or one HLA-A antigens, respectively, among patients without any acute rejection episode. This was significantly higher than the survival rate of 55% found in HLA-A compatible transplants (P = 0.001). In patients who had suffered from acute rejection episodes, a prolonged graft survival was also associated with HLA-A mismatching in HLA-B,DR mismatched transplants (P = 0.04). The beneficial effect on graft survival of HLA-A mismatching was most pronounced in patients treated with high/medium dose CyA and prednisolone (P = 0.004 overall and P = 0.0007 for HLA-B,DR mismatched transplants). In conclusion, HLA-A mismatching was associated with enhanced long-term renal graft survival in CyA-treated recipients of HLA-B,DR mismatched transplants. In clinical situations, the present results might, if confirmed, contribute to the prolongation of long-term graft survival. The results might indicate the existence of tolerance promoting allogeneic markers within the HLA-A class I region.