The role of beta-pleated sheet DRB1 differences in acute rejection after cadaveric kidney transplantation.

Donor-recipient HLA matching influences graft survival in kidney transplantation, and it has been widely demonstrated that cadaveric graft survival decreases with increasing HLA antigen mismatches. The analysis of HLA mismatches (MMs) suggests that HLA loci do not all have the same importance in predicting graft outcome; DR compatibility, for instance, has been shown to have an important role in graft rejection, especially in the first posttransplant months. These antigens are expressed on the dendritic cells of the transplanted organ and are responsible for both early "direct" allogenic recognition of donor cells as well as "indirect" recognition of peptides from donor HLA molecules presented by the recipient's DR antigens.The compatibility for HLA-A and -B antigens (present on all graft cells), conversely, has been shown to be important both early on in the posttransplant period and later.The role of the DP locus is still controversial, but it would appear to be involved in retransplants in hyperimmunized subjects.1 In contrast, it is well-known that HLA compatibility influences cellular (CTLs) and humoral (anti-HLA-non-self antibodies) alloreactivity toward the graft.2, 3Although matching for HLA alleles may enhance long-term graft survival,4 the extensive heterogeneity of the HLA system5 means that few kidneys are well-matched. Conversely, some kidney transplants from cadaveric donors have shown good long-term graft survival despite poor HLA compatibility. This apparent contradiction is probably due to the fact that most of the alleles show 95% similarity in sequence and structure, antigenic differences being determined by a relatively restricted number of amino acid residues responsible for the conformation of the peptide-binding groove. Published work has shown that some HLA antigenic subtypes can be immunogenic when confronted with certain antigens but permissive for recipients with other HLA antigens.6 For this reason alternative approaches to HLA matching such as "epitope," cross-reactive groups (CREG), and "residue" matching were developed to discover permissive mismatches.7, 8, 9 Sequence studies of HLA class I and class II loci have shown that different alleles have similar amino acid residues and that serologically identical antigens may have differing nucleotide and amino acid sites.The aim of this study, on the basis of the above, was to analyze the correlation between DRB1 amino acid residue matching in cadaveric renal transplants, the occurrence of acute rejection episodes, and the posttransplant donor-specific humoral response.