title: Neutrophil cytoplasmic antibodies (p-ANCA) in ulcerative colitis.
abstract: OBJECTIVE
  To study ulcerative colitis associated neutrophil cytoplasmic antibodies (p-ANCA) in respect of class and subclass distribution, antigen specificity, and (sub)cellular localisation of the antigen(s) to which these antibodies are directed.
  
  
  METHODS
  p-ANCA positivity was determined using the standard indirect immunofluorescence test (IIFT). The immunoglobulin (Ig) subclass distribution of p-ANCA was investigated using monoclonal antibodies directed against IgG1, IgG2, IgG3, and IgG4. Intracellular antigen localisation studies were performed on (fractionated) neutrophils using antigen-specific antibodies.
  
  
  RESULTS
  In contrast to vasculitis associated ANCA, ulcerative colitis p-ANCA are mainly of IgG1 and IgG3 subclass and lack IgG4. Ulcerative colitis p-ANCA are myeloid specific. IIFT data indicate that the related antigen(s) seem(s) to be located not in the cytosol, but in the granules (most likely the azurophil granules) of the neutrophil.
  
  
  CONCLUSIONS
  p-ANCA in ulcerative colitis have a different immunoglobulin subclass distribution than the ANCA of systemic necrotising vasculitis and necrotising and crescentic glomerulonephritis. This may point to differences in immune regulation between these diseases. Both cathepsin G and lactoferrin are recognised by a subpopulation of ulcerative colitis p-ANCA. In our series, eight out of 36 (22%) of ulcerative colitis associated p-ANCA react with lactoferrin and seven (19.5%) other sera with cathepsin G. None of them recognised both antigens. The main target antigen(s) of ulcerative colitis p-ANCA still remain(s) to be identified.
authors.affiliation: Department of Immunological Haematology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: P M
authors.initials: PM
authors.lastname: Ellerbroek
authors.forename: M
authors.initials: M
authors.lastname: Oudkerk Pool
authors.forename: B U
authors.initials: BU
authors.lastname: Ridwan
authors.forename: K M
authors.initials: KM
authors.lastname: Dolman
authors.forename: B M
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: A E
authors.initials: AE
authors.lastname: von dem Borne
authors.forename: S G
authors.initials: SG
authors.lastname: Meuwissen
authors.forename: R
authors.initials: R
authors.lastname: Goldschmeding
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056649:Cathepsin G; D002403:Cathepsins / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology*; D003594:Cytoplasmic Granules / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007781:Lactoferrin / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D012697:Serine Endopeptidases
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D002403:Cathepsins; D007781:Lactoferrin; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G