Anti-Integrin αvβ6 Autoantibodies as a Biomarker for Ulcerative Colitis in Patients with Axial Spondyloarthritis

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Objectives An association between axial spondyloarthritis (axSpA) and inflammatory bowel diseases (IBD) has been well described. IgG autoantibodies against the integrin avb6 have been recently identified in the serum of patients with the ulcerative colitis (UC) form of IBD with a high sensitivity and specificity.[1,2] These anti-integrin avb6 autoantibodies (AIA) have also been discovered in patients with primary sclerosing cholangitis, another disease associated with UC.[3] We sought to determine if AIAs could similarly be found in axSpA patients with IBD or with axSpA alone and to evaluate the potential of AIA as a diagnostic test for gut involvement in axSpA patients. Methods Using a previously published ELISA protocol we measured AIA levels in sera of patients with (i) axSpA and UC (n=18), (ii) axSpA and Crohn’s Disease (CD) (n=29), (iii) axSpA alone (n=48), and healthy controls (n=48).[2] The mean + 3 SD ELISA absorbance of the healthy controls was used as a cutoff for AIA positivity. Clinical variables were compared between AIA+ and AIA− patients. Longitudinal serum samples were analyzed to determine if AIA levels changed over time or with biologic use, and if AIA levels correlated with any markers of axSpA severity. Results Patients with axSpA and UC showed a significant increase in mean absorbance compared with axSpA alone and with healthy controls (Figure 1A). 56% of patients with axSpA and UC were AIA+, compared to 26% of patients with axSpA and CD, 4% of patients with axSpA alone, and 0% of healthy controls. For diagnosis of UC among axSpA patients, this test had a sensitivity of 55.6%, specificity of 89.6%, positive likelihood ratio of 5.35 and negative likelihood ratio of 0.50. Receiver operating characteristic analysis of this test yielded an area under curve value of 0.83 as a test for UC in axSpA patients (Figure 1B). AIA positive status was associated with a family history of axSpA, a family history of IBD and, surprisingly, a decreased maximum CRP and BASDAI. While 2/4 AIA+ patients seroconverted following biologic treatment, AIA levels were generally consistent over time and did not seem to trend with CRP or BASDAI. Conclusion We found that within axSpA patients, AIA demonstrated potential as a diagnostic test for UC, and may particularly be useful in screening axSpA patients with a family history of axSpA or IBD. To our knowledge, this is the first study to date to examine AIA in axSpA. [1.] Kuwada T. Gastroenterology 2021;160;2383-2394.e2. [2.] Livanos A. Gastroenterology 2023;164;619-629. [3.] Yoshida H. J Gastroenterol 2023;58:778-789. Best Abstract on Clinical or Epidemiology Research by a Trainee – Phil Rosen Award

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