Influence of HLA-DRB1* incompatibility on the occurrence of rejection episodes and graft survival in serologically HLA-DR-matched renal transplant combinations

BACKGROUND: The aim of the present study was to analyze the effect of HLA-DRB1* mismatches on graft function and graft survival in 92 patients who received serologically HLA-DR split antigen-matched cadaveric renal transplants. METHODS: The polymorphic second exon of the HLA-DRB1 alleles was typed using the sequence-specific oligonucleotides technique. RESULTS: The results show that in 26 of the 92 analyzed combinations, one or more HLA-DRB1* mismatches were found (28%). The analysis of the occurrence of treatable rejection episodes during the first 3 months after transplantation demonstrated a significantly higher incidence of rejection episodes in the HLA-DRB1*-mismatched group: 18 of 26 (69%) in the HLA-DRB1*-mismatched group against 23 of 66 (35%) in the HLA-DRB1*-matched group (P(uncorr)=0.0033). However, no effect of HLA-DRB1* mismatches on graft survival was found, although in general graft survival in the whole patient group was negatively influenced by the occurrence of rejection episodes during the first 3 months after transplantation (P(uncorr)=0.0008). In contrast, in the HLA-DR4-matched donor-recipient combinations (n=28), the effect of mismatching for the HLA-DRB1*04 alleles seemed to have a pronounced effect not only on the occurrence of rejection episodes but also in the form of diminished graft survival. CONCLUSIONS: Thus, this study indicates that the existence of HLA-DRB1* allele mismatches in renal transplant recipients, matched for the serologically defined HLA-DR split antigens, is not harmful for the transplant. The exception is the HLA-DRB1*04 mismatch, which seems to be deleterious for the grafted organ