Anti-integrin αvβ6 autoantibodies are increased in PSC patients with concomitant IBD and correlate with liver disease severity
Clinical Gastroenterology and Hepatology, 2024
Bloemen H., Livanos A., Martins A., Dean R., Bravo A., Bourgonje A., Tankelevich M., Herb J., Cho J., Santos A., Rodrigues C., Petralia F., Colombel J., Bowlus C., Schiano T., Torres J., Levy C., Mehandru S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Hepatology | Pathophysiology | Blood | O Olink Target 96 |
Abstract
Background and aims
Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity.
Methods
Four cohorts of pre-liver transplant PSC patients were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HC) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Olink® inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity.
Results
A total of 137 PSC patients (including 76 with PSC-UC, 33 with PSC-Crohn’s disease (CD) and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HC) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared to PSC alone (p<0.0001 and 0.003) and HC (p<0.0001 and p<0.0001). However, anti-αvβ6 levels in PSC alone were not increased compared to HC. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity including alkaline phosphatase level (r=0.32, p=0.004), the revised Mayo PSC risk score (r=0.25, p=0.02) and liver stiffness measurement (r=0.43, p=0.008) after adjusting for age, gender, race/ethnicity and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling.ConclusionAnti-αvβ6 autoantibodies identify a subset of PSC patients with concomitant IBD.