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.

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.

Figure 1

Levels of anti-Saccharomyces cerevisiae antibody (ASCA) positive sera from the Crohn's disease (CD) population. The solid line in each group represents the mean of the subgroup. Almost all patients (25/26) expressing the highest levels of either IgG or IgA ASCA (⩾100 EU/ml, values above the broken line) were part of the CD subgroup expressing both IgG and IgA ASCA.

Figure 2

Substratification using selected expression of immune markers. Disease behaviour characteristics were examined in more immunologically homogeneous subgroups of patients with Crohn's disease (CD) (those expressing high levels of a single marker antibody) and compared with all other CD study patients. Overall differences in proportions were evaluated using the χ² test for trend (p<0.001 for each of the disease behaviour characteristics).

Figure 3

Surgery as a measure of disease aggressiveness. Substratification of the subset of patients with small bowel disease (Crohn's disease (CD) involving the small bowel alone or in combination with the colon) using selective immune marker expression. (A) Percentage of patients requiring small bowel surgery and (B) total number of small bowel surgeries per patient with small bowel involvement. Overall differences in proportions were evaluated using the χ² test for trend. (A: p<0.0001; B: p<0.005).