title: The perfect storm: HLA antibodies, complement, FcγRs, and endothelium in transplant rejection.
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.
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Kimberly A
authors: KA
authors: Thomas
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Nicole M
authors: NM
authors: Valenzuela
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ereed@mednet.ucla.edu.
authors: Elaine F
authors: EF
authors: Reed
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D004727:Endothelium / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D017452:Receptors, IgG; D003165:Complement System Proteins
keywords: HLA antibodies; antibody-mediated rejection; classical complement pathway; organ transplantation