HLA-DPA1 and -DPB1 antibodies in kidney transplant candidates

All preformed HLA antibodies have a deleterious impact on kidney graft outcome but current HLA class II matching strategies for kidney transplantation only consider the DR antigens. As for DQ molecules, both alpha and beta chains of DP heterodimers are polymorphic and can elicit a humoral immune response. In 206 renal transplant candidates showing production of HLA class II antibodies, we investigated the incidence of anti- DP alloantibodies by Luminex Single Antigen Beads coated with 24 DPA1/DPB1 heterodimers (6 DPA1 and 20 DPB1 alleles variously combined with each other). Analyzing the beads' reaction patterns in relation to amino acid sequences of the antibodyreactive alleles, we also investigated the putative epitopes for DPA1 and DPB1 antibody formation. Seventy-seven (37%) of the HLA class II positive patients showed anti-DP antibodies; 53 of these (69%) had anti-DPB1 antibodies, 2 (3%) had anti-DPA1 and the remaining 22 (28%) patients had both anti-DPA1 and-DPB1. Of the sensitized anti-DP positive patients, 70% of them had had a previous transplant, 23% had had pregnancies and 7% received transfusions only. The two patients who showed only production of anti-DPA1 antibodies were sensitized by a previous transplant. Analyzing epitopes whose recognition determined antibody formation, we identified 3 putative epitopes for anti-DPA1 antibody patterns (30Q/111R, 50R/127P/160V, 50Q). Ten putative epitopes for anti-DPB1 antibody patterns were identified (33-36E-FA, 33-36E-FV, 33-36E-LV, 55-57AAE, 55-57DED, 55-57DEE, 84- 87DEAV, 84-87GGPM, 84-87VGPM, 194Q). Twenty-five (33%) of the anti-DPB1 positive patients developed antibodies which could be grouped in more than one antibody patterns corresponding to different epitopes. This study confirms that both alpha and beta chain epitopes of HLA-DP molecules are immunogenic. The most important stimulus for anti-DP antibody production was a previous transplant, but also pregnancies and transfusions determined the development of anti-DP alpha/beta chain specific antibodies. Consequently, in renal transplantation, HLA matching strategies should consider all the class II molecules especially for retransplant patients.