Antigen specificity of circulating anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease.
OBJECTIVE
To characterize the antigen specificity of circulating anti-neutrophil cytoplasmic antibodies (ANCAs) in inflammatory bowel disease (IBD).


METHODS
Analysis of the prevalence of circulating ANCAs in patients with ulcerative colitis and Crohn's disease, by both non-specific methods (immunofluorescence against fixed neutrophil leukocytes) and specific antigen techniques (against purified neutrophil leukocyte constituents).


METHODS
Indirect immunofluorescence against fixed polymorphonuclear leukocytes, and solid-phase enzyme-linked immunosorbent assay (ELISA) against neutrophil constituents (alpha-granules, elastase, myeloperoxidase, cathepsin g, lysozyme and lactoferrin).


RESULTS
Although results using immunofluorescence were typical of other studies (ulcerative colitis positive in 41%, Crohn's disease in 10%), ELISA studies showed antibody activity against neutrophil components in 69% of patients with ulcerative colitis and 39% of those with Crohn's disease. Antibodies in ulcerative colitis were commonly directed (in descending order) against lysozyme, cathepsin G, elastase, and lactoferrin, and in Crohn's disease against lysozyme.


CONCLUSIONS
Correlation of indirect immunofluorescence data and ELISA results indicated that even this large panel of specific antigens fails to identify all the ANCA targets in IBD. The lack of correlation between the findings of ANCAs, either in general or versus a specific target, and disease extent or activity in ulcerative colitis supports the suggestion that ANCAs are unlikely to be of primary importance in pathogenesis.
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D056649:Cathepsin G; D002403:Cathepsins / Q000276:immunology; D015209:Cholangitis, Sclerosing / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D003594:Cytoplasmic Granules / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007781:Lactoferrin / Q000276:immunology; D019272:Leukocyte Elastase; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010196:Pancreatic Elastase / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D012697:Serine Endopeptidases; D014657:Vasculitis / Q000276:immunology
D000906:Antibodies; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D009195:Peroxidase; D009113:Muramidase; D002403:Cathepsins; D007781:Lactoferrin; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase