79-P

Abstract

To investigate the correlation of HLA alloepitopes with the development of de novo donor specific antibodies ( dn DSA) after renal transplantation. High resolution HLA-DR and HLA-DQ typing of 31 recipients with dn DSA and their donors was performed using sequence specific oligonucleotide probes. HLAmatchmaker software was used to determine eplet mismatches (MM). The mismatched eplet load for donor recipient pairs and the immunodominance of each eplet MM was analyzed. Dn DSA developed against HLA-DR (n = 14), HLA-DQ (n = 22), or both (n = 5). Mean traditional HLA antigen mismatch was not predictive of dn DSA development at HLA-DR (1.1 MM vs. 1.4 MM, p = 0.36) (Fig. 1) or HLA-DQ alpha/beta (1.6 MM vs. 2.2 MM, p = 0.06). However, those who developed dn DSA had a greater number of locus specific mismatched eplets at HLA-DR (11.2 MM vs. 17.4 MM, p = 0.05) and HLA-DQ (7.3 MM vs. 26 MM, p < 0.01). There were 5 HLA-DR eplets and 19 HLA-DQ (alpha chain n = 9, beta chain n = 10) (Fig. 2) eplets which were significant univariate predictors of dn DSA development against HLA-DR or HLA-DQ respectively. Eplet load was a better predictor of dn DSA development compared to traditional HLA matching at the Class II HLA-DR and HLA-DQ loci. Further study will be needed to evaluate whether these immunodominant epitopes predict dn DSA development in a multivariate model.