Association between specific HLA combination and probability of acute graft versus host desease in bone marrow transplantation

The clinical results of related and unrelated donor bone marrow transplantation are continually improving reflecting best matching in HLA typing, GvHD prophylaxis and transplantation in a favourable phase of disease. However, matching each HLA allele may or may not be critical for successful stem cell transplantation. Some degree of HLA mismatch ("permissible" mismatches) may be tolerated, especially in children. In fact, mismatched donor antigens are differentially recognised depending on the HLA phenotype of the recipient. The findings may have important clinical consequences, after transplantation, for graft survival and GvHD. As known, a large fraction of HLA class I, and possibly class II, molecules can be classified into relative few supertypes, characterised by overlapping peptide-binding repertoires and consensus B- and F-pocket structures. Recent data suggest that the majority of HLA -A and -B alleles in human population can be grouped into four major supertypes, as defined by their broad peptide-binding specificities. In order to confirm that an association between a specific HLA combination and a GvHD exists, we studied 22 couples of unrelated donor-recipient bone marrow transplantation. We performed HLA -A and-B high resolution typing by sequencing analysis finding a acute GvHD when bone marrow transplantation is mismatched for different supertypes. © 2001 Blackwell Science Ltd.