Measurement of Serum IgG Anti-Integrin αvβ6 Autoantibodies Is a Promising Tool in the Diagnosis of Ulcerative Colitis

Abstract

IgG anti-integrin αvβ6 autoantibodies (IgG anti-αvβ6) have been described as highly sensitive and specific markers of ulcerative colitis (UC) in the sera of Japanese inflammatory bowel disease (IBD) patients. We aimed to evaluate the diagnostic performance of IgG anti-αvβ6 as a biomarker in Swedish patients with IBD or irritable bowel syndrome (IBS). The study included adult UC (n = 59), Crohn’s disease (CD, n = 38), and IBS patients (n = 100). Partial Mayo score and Harvey–Bradshaw index were used to assess disease severity for UC and CD, respectively. Serum levels of IgG anti-αvβ6, reported as absorbance units (AU), were measured using an in-house ELISA where the 95th percentile of 76 healthy controls defined positivity. Faecal calprotectin (fCP) was measured using a commercial assay. The majority of the IBD patients were on medical treatment, and many were in remission (UC: 40.7%; CD: 47.4%). Seventy-one percent of the UC patients, 74.2% of CD patients, and 23.1% of the IBS patients had fCP test results >50 mg/kg. The UC group had significantly higher IgG anti-αvβ6 levels (median: 1.76 AU) than the CD and IBS groups (0.34 and 0.31 AU, both p < 0.0001). The diagnostic sensitivity of IgG anti-αvβ6 in UC was 76.3%, and the specificities were 79.0% (vs. CD) and 96.0% (vs. IBS). The IgG anti-αvβ6 levels related to disease severity of the UC patients (p < 0.01–0.05). Our study shows that IgG anti-αvβ6 is associated with UC in Swedish IBD patients and that the levels of the autoantibodies reflect disease severity. IgG anti-αvβ6 could be an attractive complement to fCP in the diagnostic work up of IBD patients.

Integrin β6 deficiency protects mice from experimental colitis and colitis-associated carcinoma by altering macrophage polarization

“…Rydell et al. found that the level of serum IgG anti-integrin αvβ6 autoantibodies was obviously increased in patients with UC ( 23 ), consistent with our finding that integrin αvβ6 was abundantly expressed in the intestinal epithelium of UC. We also found integrin αvβ6 expression was related with the severity of inflammation, in accordance with the previous report which through ITGB6 transgenic mouse model found that integrin β6 maintained the colon hyperresponsive to inflammatory factors and ultimately promoted the development of IBD ( 10 ).…”

Anti-integrin αvβ6 autoantibodies are a novel predictive biomarker in ulcerative colitis

“…In a study from Japan, anti-integrin αvβ6 (anti αvβ6) autoantibodies had a sensitivity of 92.0% and a specificity of 94.8% for diagnosing UC in adult patients as compared to non-IBD subjects 11 . These results were further confirmed in a Swedish cohort and extended to a Japanese pediatric population 12, 13 . Integrin αvβ6 is an epithelium-associated heterodimer that interacts with the extracellular matrix 14 and enables the activation of latent TGF-β, which is thought to be its primary role in vivo 15, 16 .…”

“…These results were further confirmed in a Swedish cohort and extended to a Japanese pediatric population 12,13 . Integrin αvβ6 is an epithelium-associated heterodimer that interacts with the extracellular matrix 14 and enables the activation of latent TGF-β, which is thought to be its primary role in vivo 15,16 .…”

“…Anti-αvβ6 levels were significantly higher in both the COMPASS and OSCCAR UC patients compared to non-IBD controls (p<0.0001) ( Figure 2A ) consistent with published data. 11, 13 ROC analysis revealed an AUC of 0.99 (95% CI 0.97-1.00 for COMPASS) and AUC 0.96 (95% CI 0.93-0.98) for OSCCAR ( Figure 2B ). With a cut-off of 0.99 (mean non-IBD + 3SD), the sensitivity of anti-αvβ6 for distinguishing UC from non-IBD controls was 85.5% and 70.2% for the COMPASS cohort and for the OSCCAR cohort respectively with specificity of 98.1%.…”

“…Recent studies have highlighted a novel autoantibody against integrin αvβ6 in the serum of patients diagnosed with UC 11-13 . In a study from Japan, anti-integrin αvβ6 (anti αvβ6) autoantibodies had a sensitivity of 92.0% and a specificity of 94.8% for diagnosing UC in adult patients as compared to non-IBD subjects 11 .…”