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THE ROLE OF HLA-DP IN RENAL TRANSPLANTATION.
A.J. Barker , J.A. Davidson , H.J. Moore , S. Martin and P.A. Dyer . 1 Transplantation Laboratory, Manchester Royal Infirmary, Manchester, United Kingdom .
Background: Between 1st September 1990 and 31st December 2003, 1818 kidney alone transplants were carried out at our centre. 225 of these had zero mismatches at HLA-A, -B and -DR loci forming an ideal group in which to study the influence of -DP.
Methods: DNA was available for 142 donor/recipient pairs. 129 of these were from deceased and 13 were from living donors. There were 97 first, 30 second, 14 third and one fourth transplant. HLA-DPA1 typing was by PCR-SSP (DynalBiotech). HLA-DPB1 typing was performed using either PCR-SSP (Dynal
Biotech) or a PCR-SSOP Luminex based method (LIFEMATCH
HLA-SSO, Tepnel Lifecodes). Outcome measures were transplant failure, defined as either graft loss or death of the patient, and biopsy proven acute rejection (AR).
Results: Frequencies of DPA1 and DPB1 alleles were as expected in both recipients and donors, with DPA1*0103 and DPB1*0401 the most frequent. The frequency of mismatches at DPA1 (24.6%) and DPB1 (76.8%) in this cohort reflects the presence of ahot spot
of recombination between HLA-DR/-DQ and HLA-DP. At the time of the study, 79.6% of the 142 recipients had functioning transplants. There was no association between graft survival (GS) and DPA1 mismatches. Estimates of GS at five years for transplants with and without DPB1 mismatches were 79.8% and 96.8% respectively (log rank p = 0.03). Frequency of AR for patients with and without mismatches was 45.0% and 28.9% for DPA1; 37.8% and 13.6% for DPB1. Increased frequency of AR with DPB1 mismatches was statistically significant (chi-squared, p = 0.033).
Conclusion: Mismatching at HLA-DPB1 is an important predictor of reduced GS in transplants with zero -DR mismatches and also an indicator of increased likelihood of AR.