The role of DRB1 amino acid residue differences on donor-specific antibodyproduction and acute rejection after cadaveric renal transplant

The correlation between DRB1 amino acid residue matching, post-transplant h umoral response and acute rejection (ARj) episodes was analysed in 51 renal transplant donor-recipient pairs in order to determine new criteria for or gan assignment based on the alloreactivity of the residue within the peptid e binding groove. HLA class I and II compatibility was defined using serolo gical and genomic techniques; a sequence-based typing (SBT) was used for a higher resolution of DRB1 alleles. Humoral response was monitored in the fi rst post-transplant year using triple staining flow cytometric analysis of donor-specific antibodies (Abs). Our data showed that DRB1 residue compatib ility was always correlated to the absence of ARj while the presence of one or more aminoacid differences was associated with a similar frequency of A Rj. Analysis of the mismatched DRB1 amino acid residue localised in the bet a-pleated sheet and the alpha-helix of the DRB 1 molecule revealed that the frequency of beta-pleated sheet residue mismatches (MMs) was higher in the ARj-positive than in the ARj-negative group. A significant increase in the alpha-helix residue MMs was observed in patients with anti-class II Ab pro duction (p = 0.034). Furthermore, analysing in detail DRB 1 MMs at the leve l of single amino acid residue, we found that the frequency of the mismatch es localized in codon 9 and codon 28 in the beta-pleated sheet, as well as in codon 57 in the alpha-helix, was higher in patients who experienced ARj; on the other hand, MMs in codon 58 of the alpha-helix were more frequently associated with anti-class II Ab production. The identification of the res idues more involved in alloreactivity onset will make it possible to define the existence of "permissive" or immunogenic" allele combinations which co uld simplify and increase the chances of a successful transplant.