The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies

Abstract

The bactericidal/permeability-increasing protein (BPI) is anendotoxin-binding neutrophil leukocyte-granule protein withantibacterial and anti-endotoxin properties. A recombinant form of BPI(rBPI₂₁) has been developed and is being tested as atherapeutic agent to treat Gram-negative bacterial infections andexposure to Gram-negative bacterial endotoxin. BPI is also a targetantigen of anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANCAare present in cystic fibrosis, inflammatory bowel disease, vasculitis,and primary sclerosing cholangitis; presence of BPI-ANCA appearsassociated with a higher inflammatory disease activity and greaterorgan damage. BPI-ANCA as well as ANCA directed at otherneutrophil-granule proteins may exacerbate inflammation by nonspecificeffects of extracellular and cell-associated immune complexes. BPI-ANCAmay further worsen inflammation by reducing the ability of BPI topromote clearance of Gram-negative bacteria and bacterial-associatedendotoxin.

anti-neutrophil cytoplasmic autoantibodies, neutrophil granule proteins, Gram-negative bacteria, lipopolysaccharides