Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis
Hiroyuki Yoshida, Masahiro Shiokawa, Takeshi Kuwada, Yuya Muramoto, Sakiko Ota, Yoshihiro Nishikawa, Hirona Maeda, Nobuyuki Kakiuchi, Kanako Okamoto, Hajime Yamazaki, Masataka Yokode, T Nakamura, Shimpei Matsumoto, Tomonori Hirano, Hirokazu Okada, Saiko Marui, Yuko Sogabe, Tomoaki Matsumori, Atsushi Mima, Norimitsu Uza, Yuji Eso, Atsushi Takai, Ken Takahashi, Yoshihide Ueda, Yuzo Kodama, Tsutomu Chiba, Hiroshi Seno
Abstract
BACKGROUND: Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown. METHODS: The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. RESULTS: Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls (P < 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) (P = 0.008). Integrin αvβ6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvβ6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif. CONCLUSIONS: Autoantibodies against integrin αvβ6 were detected in most patients with PSC; anti-integrin αvβ6 antibody may serve as a potential diagnostic biomarker for PSC.