Fig. 5.

Blocking of integrin αvβ6-fibronectin binding by IgG of patients with PSC. a Inhibition of integrin αvβ6 binding to fibronectin by IgG from a patient with PSC was examined using a solid-phase binding assay. The cutoff OD, defined as the mean plus three standard deviations of the control IgG, is indicated by a dashed line. The assay showed that IgGs of 15/37 (40.5%) patients with PSC but none of the control IgGs blocked the binding of integrin αvβ6 to fibronectin. b Dose-dependent inhibition of binding of integrin αvβ6 to fibronectin by PSC patient IgG. IgGs of the patients with PSC with the anti-integrin αvβ6 antibody (PSC 21, 19, 17, 29, 32, 26, 1, 2, and 3) inhibited integrin αvβ6–fibronectin binding in a dose-dependent manner. Conversely, IgGs of controls with the anti-integrin αvβ6 antibody (IgG4-SC 7 and CCC 21) and a healthy control (HC 3) exhibited no blocking activity. c Titers of IgG antibodies against integrin αvβ6 were correlated with the blocking activity of integrin αvβ6-fibronectin binding (r = 0.72, P < 0.001). d, e Peptide RGDS (Arg–Gly–Asp–Ser) (d), but not RGES (Arg–Gly–Glu–Ser) (e), impaired binding of IgG from patients with PSC to integrin αvβ6 in a dose-dependent manner. We used the RGDS and RGES peptides to represent the RGD and RGE motifs, respectively [29]. OD optical density, IgG immunoglobulin G, PSC primary sclerosing cholangitis, IgG4-SC IgG4-related sclerosing cholangitis, CCC cholangiocellular carcinoma