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RESEARCH PRODUCT

P046 Deconstructing HLA-C mismatch in hematopoietic stem cell transplantation

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Contrary to other HLA loci, allele vs antigen mismatches in HLA-C appear to differentially impact HSCT outcome. Aim of this study was to investigate the independent role of other factors characterizing a patient’s HLA-C non-shared allele, in HSCT outcome as well as their distribution in allele vs antigen mismatched cases. 288 9/10 HLA-C mismatched unrelated transplant pairs, were additionally genotyped by sequence based typing for rs9264942(C/T) and rs67384697(ins/del), which are considered surrogate markers of HLA-C expression levels. A proxy MFI model as previously described (Petersdorf et al., Blood 2014), was also implemented in the analysis. All patient non-shared alleles were characterized in regard to mismatch level, expression-relevant polymorphisms’ genotype and proxy MFI levels as well as differences in residues 77, 80 (C1/C2 KIR epitopes) and 116 (immunogenic spot). In order to assess the independent impact of each factor on HSCT outcome, overall survival, disease free survival, non-relapse mortality and relapse incidence were set as endpoints. The balance in distribution of the aforementioned parameters in allele vs antigen mismatched cases was estimated by Chi-square and Wilcoxon tests. Data analysis revealed no statistically significant impact of any of the parameters tested individually on HSCT outcome. Their distribution with respect to mismatch level, however, was markedly skewed. Antigen mismatches were associated with more highly-expressed HLA-C alleles according to the MFI proxy model as well as the rs9264942C and rs67384697del genotypes (MFI: p