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Gut 47:487-496 doi:10.1136/gut.47.4.487
  • Inflammatory bowel disease

Marker antibody expression stratifies Crohn's disease into immunologically homogeneous subgroups with distinct clinical characteristics

  1. E A Vasiliauskasa,
  2. L Y Kama,
  3. L C Karpa,
  4. J Gaienniea,
  5. H Yangb,
  6. S R Targana
  1. aDepartment of Medicine, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, CA 90048, USA, bDepartment of Pediatrics, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, CA 90048, USA
  1. Dr E A Vasiliauskas or Dr S R Targan, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8631 W Third Street Suite 430E, Los Angeles, CA 90048, USA. Email: Eric.A.Vasiliauskas{at}cshs.org orStephan.Targan{at}cshs.org
  • Accepted 12 April 2000

Abstract

BACKGROUND Perinuclear antineutrophil cytoplasmic antibodies (pANCA) have been detected in a clinically distinct Crohn's disease subpopulation. Antibodies toSaccharomyces cerevisiae (ASCA) have been demonstrated in the majority of patients with Crohn's disease.

AIMS 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.

Footnotes

  • Abbreviations used in this paper:
    ASCA
    anti-Saccharomyces cerevisiae antibody
    CD
    Crohn's disease
    ELISA
    enzyme linked immunosorbent assay
    EU
    ELISA units
    IIF
    indirect immunofluorescent
    IBD
    inflammatory bowel disease
    pANCA
    perinuclear antineutrophil cytoplasmic antibodies
    UC
    ulcerative colitis
    TNF
    tumour necrosis factor
    PNPP
    p-nitrophenol phosphate
    Ig
    immunoglobulin