Author(s): Lucas DP, Leffell MS, Zachary AA
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Abstract BACKGROUND: Information about differences in immunogenicity of various HLA antigens may help guide donor selection and identify mismatches to avoid for patients likely to need retransplantation. To date, antibody responses to a wide array of individual mismatched antigens have not been evaluated. METHODS: Frequencies of antibodies to mismatched HLA-A, HLA-B, HLA-DR, and HLA-DQ antigens were determined for 703 renal transplant patients who had no detectable donor-specific antibody before transplantation. The impact of cross-reactive group matching and production of antibodies cross-reactive with mismatched antigens were also assessed. Antibodies were identified using multiplexed bead assays. RESULTS: The overall mean frequencies were similar for HLA-A (53.2\%), HLA-DR (52.6\%), and HLA-DQ (59.0\%) antibodies, but significantly lower for HLA-B antibodies (42.4\%). However, the response to individual antigens ranged from 15.0\% to 76.2\%. Antibody frequencies were reduced significantly for 54 of 62 specificities when the patient possessed an antigen cross-reactive with the donor mismatch, but the magnitude of the effect was variable and ranged from 8\% to 83\%. Moreover, there was directionality in the protective effect of cross-reactive group matching. Overall mean donor-specific antibody frequencies were comparable for men and women except for a significantly higher frequency of antibodies to HLA-DR among men (56.6\% vs. 47.8\%, P=0.004). Overall mean frequencies in blacks were higher than, or comparable to those of, whites, but differences were not significant. CONCLUSION: There is considerable variability in the immunogenicity of different HLA antigens that is impacted by the presence or absence of cross-reactive antigens in the patient's phenotype. This information can be used to augment the immunologic evaluation of donor-recipient pairs.
This article was published in Transplantation
and referenced in Journal of Clinical and Experimental Transplantation