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  • Identification of an Anti-Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis.

Identification of an Anti-Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis.

Gastroenterology (2021-02-15)
Takeshi Kuwada, Masahiro Shiokawa, Yuzo Kodama, Sakiko Ota, Nobuyuki Kakiuchi, Yasuhito Nannya, Hajime Yamazaki, Hiroyuki Yoshida, Takeharu Nakamura, Shimpei Matsumoto, Yuya Muramoto, Shuji Yamamoto, Yusuke Honzawa, Katsutoshi Kuriyama, Kanako Okamoto, Tomonori Hirano, Hirokazu Okada, Saiko Marui, Yuko Sogabe, Toshihiro Morita, Tomoaki Matsumori, Atsushi Mima, Yoshihiro Nishikawa, Tatsuki Ueda, Kazuyoshi Matsumura, Norimitsu Uza, Tsutomu Chiba, Hiroshi Seno
要旨

Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti-integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti-integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity.

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製品内容

Sigma-Aldrich
ヒト血漿フィブロネクチン精製タンパク質, from human plasma, liquid, 1 mg/mL (100 MG pack size is lyophilized), purified protein, suitable for cell culture
Sigma-Aldrich
Arg-Gly-Asp-Ser, ≥95% (HPLC)
Sigma-Aldrich
Arg-Gly-Glu-Ser acetate salt, ≥95% (HPLC)