TY - JOUR
T1 - The perfect storm
T2 - HLA antibodies, complement, FcγRs, and endothelium in transplant rejection
AU - Thomas, Kimberly A.
AU - Valenzuela, Nicole M.
AU - Reed, Elaine F.
N1 - Funding Information:
This work was supported by the Ruth L. Kirschstein National Research Service Award T32HL69766 (to K.A.T.) and the National Institute of Allergy and Infectious Diseases Grant R01AI042819 (to E.F.R.). The authors thank A. Roux and M. Rossetti for critical review of the manuscript.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Antibody-mediated rejection
KW - Classical complement pathway
KW - HLA antibodies
KW - Organ transplantation
UR - http://www.scopus.com/inward/record.url?scp=84929050262&partnerID=8YFLogxK
U2 - 10.1016/j.molmed.2015.02.004
DO - 10.1016/j.molmed.2015.02.004
M3 - Review article
C2 - 25801125
AN - SCOPUS:84929050262
VL - 21
SP - 319
EP - 329
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
SN - 1471-4914
IS - 5
ER -