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(Journal of Leukocyte Biology. 2001;69:505-512.)
© 2001 by Society for Leukocyte Biology

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

H. Schultz^*, J. Weiss, S. F. Carroll and W. L. Gross^*

^* Department of Rheumatology, University of Lübeck, Rheumaklinik Bad Bramstedt GmbH, Bad Bramstedt, Germany;
Deparment of Internal Medicine, Division of Infectious Diseases, University of Iowa, Iowa City, Iowa, and Iowa City VAMC, Iowa City, Iowa; and
XOMA (US) LLC, Preclinical Research, Berkeley, California

Correspondence: H. Schultz, Department of Rheumatology, University of Lübeck, Rheumaklinik Bad Bramstedt GmbH, P.O. Box 1448, D-24572 Bad Bramstedt, Germany. E-mail: HSchultzMD{at}aol.com

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.

Key Words: anti-neutrophil cytoplasmic autoantibodies • neutrophil granule proteins • Gram-negative bacteria • lipopolysaccharides

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