Abstract
We report a case of a 36year old Caucasian G4P4 female with chronic kidney disease stage 4 and no prior transfusions who received a living-related kidney transplant from her brother, which was a 0A-1B-1DR mismatch. She was discharged post-operative day 4 with good allograft function and a serum creatinine (SCr) of 0.76mg/dL. Seven days later she presented with pain at the allograft site and a SCr of 3.6mg/dL. Allograft biopsy showed evidence of thrombotic microangiopathy, hemorrhagic cortical necrosis, and peritubular capillary positivity for C4d. This strongly suggested an acute antibody mediated rejection (AMR), which was later corroborated by histology of the post-nephrectomy allograft specimen. HLA antibody screen at the time of AMR by single-antigen beads demonstrated a broad pattern of reactivity against all beads expressing Bw6-associated antigens and multiple HLA-C antigens. The MFI values of all Bw6-associated beads were above 15000 when tested at 1:25 dilution; MFI of the donor specific antibody against B62 (Bw6) was 19366. Only low-level reactivity against a small number of HLA-B antigens was detected prior to transplantation either with neat serum or at 1:25 dilution. These findings are consistent with an anamnestic alloantibody response against a common epitope present in HLA-B and HLA-C antigens, initially primed by exposure to her husband’s antigens during pregnancy and rechallenged by renal transplantation. HLA typing of the patient’s husband demonstrated no antigen mismatch at the A or B loci and one antigen mismatch at the C locus (patient is C16 and her husband is C14). Notably, C14 and all Bw6-associated antigens share a confirmed epitope, 80N (HLA epitope registry). This case demonstrates an unusual incidence of sensitization to Bw6-associated antigens via exposure to a Bw6-crossreactive C antigen. It also highlights the risk of occult alloimmunization that is undetectable in pre-transplant HLA antibody testing but may cause rapidly progressive allograft rejection.