Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

Hum Immunol. 2014 Aug;75(8):703-8. doi: 10.1016/j.humimm.2014.04.001. Epub 2014 Apr 19.

Abstract

Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA.

Keywords: Antibody-mediated rejection; Donor-specific antibodies; Epitopes; Flow cytometry crossmatch; Kidney transplantation.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Complement C1q / metabolism
  • Complement C4b / metabolism
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / metabolism
  • Graft Rejection / pathology
  • Graft Rejection / surgery
  • HLA-DP Antigens / immunology*
  • HLA-DP alpha-Chains / immunology*
  • HLA-DP beta-Chains / immunology
  • HLA-DRB3 Chains / immunology
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / biosynthesis*
  • Kidney / immunology
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / surgery
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation*
  • Peptide Fragments / metabolism
  • Unrelated Donors
  • Young Adult

Substances

  • HLA-DP Antigens
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • HLA-DPA1 antigen
  • HLA-DPB1 antigen
  • HLA-DRB3 Chains
  • Isoantibodies
  • Peptide Fragments
  • Complement C1q
  • Complement C4b
  • complement C4d