title: The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies.
abstract: The bactericidal/permeability-increasing protein (BPI) is an endotoxin-binding neutrophil leukocyte-granule protein with antibacterial and anti-endotoxin properties. A recombinant form of BPI (rBPI21) has been developed and is being tested as a therapeutic agent to treat gram-negative bacterial infections and exposure to gram-negative bacterial endotoxin. BPI is also a target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANCA are present in cystic fibrosis, inflammatory bowel disease, vasculitis, and primary sclerosing cholangitis; presence of BPI-ANCA appears associated with a higher inflammatory disease activity and greater organ damage. BPI-ANCA as well as ANCA directed at other neutrophil-granule proteins may exacerbate inflammation by nonspecific effects of extracellular and cell-associated immune complexes. BPI-ANCA may further worsen inflammation by reducing the ability of BPI to promote clearance of gram-negative bacteria and bacterial-associated endotoxin.
authors: Department of Rheumatology, University of Lübeck, Rheumaklinik Bad Bramnstedt GmbH, Germany. HSchultzMD@aol.com
authors: H
authors: H
authors: Schultz
authors: J
authors: J
authors: Weiss
authors: S F
authors: SF
authors: Carroll
authors: W L
authors: WL
authors: Gross
mesh_terms: D000328:Adult; D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D000918:Antibody Specificity; D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D001798:Blood Proteins / Q000737:chemistry / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016207:Cytokines / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005544:Forecasting; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D015337:Multicenter Studies as Topic; D009504:Neutrophils / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D014657:Vasculitis / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens; D001798:Blood Proteins; D016207:Cytokines; D004731:Endotoxins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C021623:bactericidal permeability increasing protein