title: Marker antibody expression stratifies Crohn's disease into immunologically homogeneous subgroups with distinct clinical characteristics.
abstract: BACKGROUND
  Perinuclear antineutrophil cytoplasmic antibodies (pANCA) have been detected in a clinically distinct Crohn's disease subpopulation. Antibodies to Saccharomyces cerevisiae (ASCA) have been demonstrated in the majority of patients with Crohn's disease.
  
  
  OBJECTIVE
  To examine the relationship between selective marker antibody expression in Crohn's disease and disease onset, location, and clinical behaviour patterns.
  
  
  METHODS
  Sera from 156 consecutive patients with established Crohn's disease were evaluated in a blinded fashion for the presence of ASCA and ANCA. Clinical profiles were generated by investigators blinded to immune marker status.
  
  
  RESULTS
  Using multiple regression analyses, higher ASCA levels were shown to be independently associated with early age of disease onset as well as both fibrostenosing and internal penetrating disease behaviours. Higher ANCA levels were associated with later age of onset and ulcerative colitis-like behaviour. Substratification of the Crohn's disease population using selective ANCA and ASCA expression (high levels of a single marker antibody): (1) distinguished homogeneous subgroups that manifested similar disease location and behaviours; and (2) identified patients with more aggressive small bowel disease.
  
  
  CONCLUSIONS
  The findings suggest that by taking into account the magnitude of the host immune response, Crohn's disease can now be stratified on an immunological basis into more homogeneous clinically distinct subgroups, characterised by greater uniformity among anatomical distribution of disease and disease behaviour.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, CA 90048, USA. Eric.A.Vasiliauskas@cshs.org
authors.forename: E A
authors.initials: EA
authors.lastname: Vasiliauskas
authors.forename: L Y
authors.initials: LY
authors.lastname: Kam
authors.forename: L C
authors.initials: LC
authors.lastname: Karp
authors.forename: J
authors.initials: J
authors.lastname: Gaiennie
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: S R
authors.initials: SR
authors.lastname: Targan
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D000908:Antibodies, Fungal / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000145:classification / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012441:Saccharomyces cerevisiae / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000908:Antibodies, Fungal; D015415:Biomarkers