The perfect storm: HLA antibodies, complement, FcγRs, and endothelium in transplant rejection

Kimberly A. Thomas, Nicole M. Valenzuela, Elaine F. Reed

Research output: Contribution to journalReview articlepeer-review

80 Scopus citations

Abstract

The pathophysiology of antibody-mediated rejection (AMR) in solid organ transplants is multifaceted and predominantly caused by antibodies directed against polymorphic donor human leukocyte antigens (HLAs). Despite the clearly detrimental impact of HLA antibodies (HLA-Abs) on graft function and survival, the prevention, diagnosis, and treatment of AMR remain a challenge. The histological manifestations of AMR reflect the signatures of HLA-Ab-triggered injury, specifically endothelial changes, recipient leukocytic infiltrate, and complement deposition. We review the interconnected mechanisms of HLA-Ab-mediated injury that might synergize in a 'perfect storm' of inflammation. Characterization of antibody features that are critical for effector functions may help to identify HLA-Abs that are more likely to cause rejection. We also highlight recent advances that may pave the way for new, more effective therapies.

Original languageEnglish
Pages (from-to)319-329
Number of pages11
JournalTrends in Molecular Medicine
Volume21
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Antibody-mediated rejection
  • Classical complement pathway
  • HLA antibodies
  • Organ transplantation

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