Anti-integrin αvβ6 antibodies may be useful in accurately diagnosing ulcerative colitis (UC) and monitoring disease activity, according to study results published in Gastroenterology.
Ulcerative colitis is the most frequently diagnosed type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in UC, specific autoantigens/antibodies have not been determined.
Using 23 recombinant integrin proteins, researchers in Japan performed enzyme-linked immunosorbent assays (ELISA) on the sera from patients with UC and control participants. They examined integrin expression and immunoglobulin G (IgG) binding in the colon tissue of patients with UC and control participants using immunofluorescence and coimmunoprecipitation, respectively.
The researchers also examined the blocking activity of autoantibodies using solid-phase binding and cell adhesion assays. Screening revealed that patients with UC had IgG antibodies against integrin αvβ6. In the training and validation groups, 103/112 (92%) patients with UC and only 8/155 (5.2%) control participants had anti-integrin αvβ6 antibodies (P <.001), resulting in a sensitivity of 92% and a specificity of 94.8% for diagnosing UC. Anti-integrin αvβ6 antibody titers coincided with UC disease activity, and IgG1 was the major subclass.
The researchers also found that patient IgG bound to the integrin αvβ6 was expressed on colonic epithelial cells. Moreover, IgG of patients with UC blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion.
One of the limitations of this study is that it was performed only in Japanese patients. In addition, in vivo animal studies have not been performed to explain the pathogenic roles of autoantibodies in patients with UC.
The authors concluded, “We found anti-integrin αvβ6 antibodies in the sera of most patients with [UC] using ELISA.”
They added, “These antibody titers coincided with UC disease activity.”
Kuwada T, Shiokawa M, Kodama Y, et al. Identification of an anti-integrin αvβ6 autoantibody in patients with ulcerative colitis. Gastroenterology. Published online February 12, 2021. doi:10.1053/j.gastro.2021.02.019