title: Antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis: defined specificities may be associated with distinct clinical features.
abstract: OBJECTIVE
  The clinical significance of antineutrophil cytoplasmic autoantibodies (ANCA) in primary sclerosing cholangitis has not been established. We investigated whether analysis of the antigenic specificities of ANCA is useful for delineating clinical subsets of the disease.
  
  
  METHODS
  Sixty-nine patients with primary sclerosing cholangitis were studied. The presence of ANCA was analyzed by indirect immunofluorescence. Antibodies directed against specific antigens--proteinase 3, myeloperoxidase, elastase, bactericidal/permeability-increasing protein, cathepsin G, and lactoferrin--were identified by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  ANCA were detected by indirect immunofluorescence in 46 (67%) patients. In antigen-specific enzyme-linked immunosorbent assays, 37 (55%) of the 69 patients had antibodies to one or more antigens: 32 (46%) had antibodies to bactericidal/permeability-increasing protein, 16 (23%) had antibodies to cathepsin G, and 15 (22%) had antibodies to lactoferrin. Only 3 patients had antibodies to proteinase 3. Antibodies to myeloperoxidase or elastase were not detected. Twenty (29%) patients had antibodies to different antigens simultaneously. ANCA as detected by indirect immunofluorescence were not significantly associated with the presence of cirrhosis nor with the coexistence of inflammatory bowel disease. However, antibodies to bactericidal/permeability-increasing protein and cathepsin G were both associated with the presence of cirrhosis, and antibodies to lactoferrin were more frequently detected in patients with primary sclerosing cholangitis in conjunction with ulcerative colitis than in those without inflammatory bowel disease.
  
  
  CONCLUSIONS
  Defined specificities of ANCA in primary sclerosing cholangitis may be related to particular clinical features of the disease.
authors.affiliation: Department of Clinical Immunology, University Hospital Groningen, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Roozendaal
authors.forename: A W
authors.initials: AW
authors.lastname: Van Milligen de Wit
authors.forename: E B
authors.initials: EB
authors.lastname: Haagsma
authors.forename: G
authors.initials: G
authors.lastname: Horst
authors.forename: C
authors.initials: C
authors.lastname: Schwarze
authors.forename: H H
authors.initials: HH
authors.lastname: Peter
authors.forename: J H
authors.initials: JH
authors.lastname: Kleibeuker
authors.forename: J W
authors.initials: JW
authors.lastname: Tervaert
authors.forename: P C
authors.initials: PC
authors.lastname: Limburg
authors.forename: C G
authors.initials: CG
authors.lastname: Kallenberg
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood* / Q000276:immunology*; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000939:Epitopes