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

The bactericidal/permeability-increasing protein (BPI) is an endotoxin-bind ing neutrophil leukocyte-granule protein with antibacterial and anti-endoto xin properties. A recombinant form of BPI (rBPI(21)) has been developed and is being tested as a therapeutic agent to treat Gram-negative bacterial in fections and exposure to Gram-negative bacterial endotoxin, BPI is also a t arget antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANC A are present in cystic fibrosis, inflammatory bowel disease, vasculitis, a nd primary sclerosing cholangitis; presence of BPI-ANCA appears associated with a higher inflammatory disease activity and greater organ damage. BPI-A NCA as well as ANCA directed at other neutrophil-granule proteins may exace rbate inflammation by nonspecific effects of extracellular and cell-associa ted immune complexes. BPI-ANCA may further worsen inflammation by reducing the ability of BPI to promote clearance of Gram-negative bacteria and bacte rial-associated endotoxin.