Specific "intra-allele" and "intra-broad antigen" human leukocyte antigen alloantibodies in kidney graft transplantation

Abstract

Human leukocyte antigen (HLA) antibodies are epitope specific and not antigen specific. This work presents a case of intra-allele (IA) sensitization. A 40-year-old-man underwent transplantion with identical "broad" DR. He was apparently not sensitized to HLA antigens by complement-dependent cytotoxicity (CDC), with one previous transplantation 15 years previously. In post-transplantation monitoring, we detected an "intra-broad antigen" (IBA) anti-DRB1*13 DSA by Luminex. We performed post-transplantation B-cell cross-matching (CM) by CDC, this being completely negative. We detected allele-specific antibodies by single antigens (SA), anti-DRB1*1303 (IBA), -DQB1*0301 (IA), -DRB1*1101, -DRB3*0101, anti-DPB1*0202, and anti-DRB1*0103. These antibodies originated from the first transplantation, HLA-DR6+ homozygous and serologically broad matched, but retrospectively typed as DRB1*1401, *1303; DRB3*0101, *0202; DQB1*0301, *0503; DPB1*0401, *0202 (mismatches in italics). However the second donor was DRB1*1301, *1401 (DR6+ homozygous); DRB3*0202; DQB1*0603, *0503; DPB1*0401 (mismatches in italic). Therefore, the stronger antibodies generated in the first transplantion (anti-DRB1*1303 and -DQB1*0301) were not specific for the specific subtypes (DRB1*1301 and -DQB1*0603) on the second transplantation. Finally, it was possible to exactly define the potential immunizing epitopes the recognition of which determined antibody production. Therefore, our patient had low titers of pretransplantation IBA and IA antibodies that were not prospectively detected by CDC. Post-transplantation with Luminex, we detected these alloantibodies, but as they were not IA and IBA DSA, they did not cause allograft injury.