From infection to autoimmunity: a new model for induction of ANCA against the bactericidal/permeability increasing protein (BPI).
Antineutrophil cytoplasmic autoantibodies against the neutrophil granule bactericidal/permeability increasing protein (BPI-ANCA) have been found in diseases of different etiologies, such as cystic fibrosis, TAP deficiency or inflammatory bowel diseases. A common feature of these conditions is the chronic or profuse exposure of the host to Gram-negative bacteria and their endotoxin. BPI plays an important role in killing Gram-negative bacteria as well as neutralization and disposal of their endotoxin. During this interaction BPI can direct the delivery of complexes which contain endotoxin and bacterial outer membrane proteins to antigen presenting cells. Based on recent findings on how complexes of endotoxin and protein antigens need to be processed by dendritic cells in order to become presented on MHC class II molecules, a model can be proposed how Gram-negative bacterial infections can be linked to the generation of autoantibodies against BPI.
Schultz
Hendrik
H
Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive SW54 GH, Iowa City, Iowa 52242-1081, USA. Hendrok-Schultz@uiowa.edu
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology*; D004731:Endotoxins / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein