Antineutrophil cytoplasm autoantibodies against bactericidal/permeability-increasing protein in inflammatory bowel disease.
BACKGROUND
Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3).


OBJECTIVE
To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease.


METHODS
ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls.


RESULTS
Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01).


CONCLUSIONS
BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.
Walmsley
R S
RS
Department of Medicine, Royal Free Hospital School of Medicine, London.
Zhao
M H
MH
Hamilton
M I
MI
Brownlee
A
A
Chapman
P
P
Pounder
R E
RE
Wakefield
A J
AJ
Lockwood
C M
CM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000276:immunology*; D016022:Case-Control Studies; D056649:Cathepsin G; D002403:Cathepsins / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D007781:Lactoferrin / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009195:Peroxidase / Q000276:immunology; D011446:Prospective Studies; D012697:Serine Endopeptidases / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D007074:Immunoglobulin G; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D009195:Peroxidase; D002403:Cathepsins; D007781:Lactoferrin; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G