Generation of Donor-Specific Anti–Human Leukocyte Antigen Antibodies after the Transplantation of a Fully Matched Kidney Allograft and Its Impact on the Selection of a Subsequent Renal Regraft: A Case Report

Abstract Detection of anti–human leukocyte antigen (HLA) antibodies and identification of their specificities represent important tasks for patients awaiting kidney allografts. Regarding patients immunized by pregnancies, transfusions, or previous transplantations of solid organs, the immunization status must be observed carefully because grafting them with HLA phenotypes recognized by their antibodies represents the main cause for hyper-acute or acute rejection episodes, often leading to transplant loss. A 10-year-old patient with end-stage renal insufficiency of HLA type A3, 25; B8, 18, (Bw6); Cw7,12; DR15,17; DR51,52; DQ2,6 received a deceased donor graft showing no HLA mismatch in 1998. It lost function after 8 years, resulting in the patient's re-entry onto the waiting list for kidney transplantation in 2006. Antibody screening detected anti-HLA-A25, A26, A34, and A66 (broad A10) antibodies using various techniques (DynaChip, Single Antigen enzyme-linked immunosorbent assay [ELISA]). Additionally, a kidney offer expressing the HLA-A25 phenotype was not acceptable for the patient due to a positive complement-dependent cytotoxicity assay (CDC)-based cross-match. The question arose whether this reactivity might be due to auto-reactive antibodies directed against the HLA-A25 phenotype. However, no auto-reactive antibodies were detectable using either the CDC-based or the antibody monitoring system-ELISA–based cross-match assays. Consequently the patient was re-examined at high resolution showing the rare HLA-A*25:14 genotype. This case showed that rare alleles may result in allele-specific antibodies directed against the common variants, thus leading to unexpected positive cross-match results against apparently matched allografts.