Accelerated humoral renal allograft rejection due to HLA-C14 mediated allosensitization to HLA-Bw6

Stephen P. Persaud, Brian Duffy, Donna L. Phelan, Thalachallour Mohanakumar, Rowena Delos Santos, Joseph P. Gaut, Chang Liu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objectives To investigate immunological mechanisms underlying accelerated antibody-mediated rejection (AMR) of a living-related renal allograft in a patient with no detectable antibodies to donor human leukocyte antigens (HLA) in pre-transplant sera. Methods Pre- and post-transplant HLA antibody specificities were determined by single-antigen bead assay, and crossmatching was performed by flow cytometry- and complement-dependent cytotoxicity-based methods. Intermediate- and high-resolution HLA typing were performed by molecular methods. Results Pre-transplant patient serum reacted weakly against Bw6-positive beads; cytotoxicity and flow crossmatches were negative. The patient was mismatched for the donor antigens B62 and C10 (Bw6-positive). Following transplantation, strong antibody responses against B62, C10, and all Bw6-positive beads were detected. This reactivity was initially masked by complement interference, but became apparent at 1:20 dilution. High-resolution typing suggested that the anti-C16 antibody reactivity detected was an allele-specific response to donor C16:01 (Bw6-positive) but not recipient C16:02 (Bw6-negative). Alloimmunization likely occurred during pregnancy, during which HLA-C14 (Bw6-positive) was the only mismatched paternal HLA Class I allele. Conclusions Sensitization to HLA-Bw6 via exposure to paternal HLA-C14 during pregnancy likely predisposed this patient to AMR. The case demonstrates the immunogenicity of HLA-C14-associated Bw6 epitopes in vivo and the clinical significance of low-level antibodies to HLA-Bw6.

Original languageEnglish
Pages (from-to)692-698
Number of pages7
JournalHuman Immunology
Volume78
Issue number11-12
DOIs
StatePublished - Nov 2017

Keywords

  • Alloimmunization
  • Crossmatch
  • HLA
  • Kidney
  • Transplantation

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