(P025) ANTI-αVβ6 AUTOANTIBODIES ARE PRESENT IN COLONIC CROHN'S DISEASE AND ASSOCIATE WITH DISEASE ACTIVITY (Posters of Distinction)

Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are present in up to 90% of patients with ulcerative colitis (UC), but there is a paucity of data regarding anti-αvβ6 in Crohn’s disease (CD). We hypothesized that anti-αvβ6 would be present in patients with colonic CD given the shared biological characteristics with UC.

We measured anti-αvβ6 IgG in 1,815 peripheral blood samples from six cohorts from both the USA and Leuven, Belgium. These cohorts represent patients with established and incident IBD as well as non-IBD controls (HC). We compared anti-αvβ6 IgG levels by disease type (UC, CD, HC) and by disease location in CD subjects (Ileal only [L1], colonic only [L2] and ileocolonic [L3]). In addition, we assessed associations with disease activity and fecal calprotectin in the Leuven cohort where data were available and pANCA in the OSCCAR cohort (Rhode Island, USA). 

We initially assessed anti-αvβ6 in adult and pediatric subjects from Mount Sinai Hospital (MSH), NY (MSCCR-adult, n= 599 and Pediatric, n=75). Anti-αvβ6 levels in UC patients were significantly higher than the levels in both CD and HC (P < 0.0001, P < 0.0001). Importantly, CD patients had higher levels compared to HC (P=0.0330) (Fig. 1A). With a cut-off based on the log₁₀ transformed mean + 2 standard deviations of HC, the seropositive rate was 64% in UC and 16% in CD versus only 2% in HC (P < 0.0001, P < 0.0001) (Fig. 1B). In the Pediatric Cohort, we observed similar results with increased seropositivity in CD (22%) compared to HC (0%) (P=0.0073) (Fig. 1C-D). Next, we examined anti-αvβ6 by CD location. Patients with L2 disease had higher levels than L1 across all cohorts (MSCCR P</em> < 0.0001, Pediatric P=0.0531) including two incident cohorts (COMPASS n=81 P < 0.0001, OSCCAR n=167 P =0.0099), while patients with L3 disease had intermediate levels (Fig. E-H). These findings were further verified in an independent cohort (n=730) using a commercially available ELISA kit (MBL) (Fig. 1I). Further, a significant positive correlation between anti-αvβ6 and pANCA was observed in L2 CD (Spearman r = 0.5207, P < 0.0001) and L3 CD (Spearman r = 0.4625, P = 0.0012) but not L1 CD (Spearman r = -0.2395, P =0.1420) (OSCCAR cohort) (Fig. 1J). Finally, in the Leuven cohort (n=163), anti-αvβ6 levels were significantly higher in those with moderate-severe disease activity (SES-CD ≥7) compared to inactive-mild disease (SES-CD 0-6) and in those with elevated fecal calprotectin (≥150μg/g) (P=0.0024, P=0.0057) (Fig. 1K+L).

In conclusion, anti-αvβ6 autoantibodies distinguish between colonic and ileal disease but not between UC and CD. Our data further supports shared immunologic signatures between colonic CD and UC that differ from ileal CD. Further understanding of these differences may help in disease classification and specificity of therapeutic targets