Dataset Information

Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis.

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.

SUBMITTER: Yoshida H

PROVIDER: S-EPMC10366314 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis.

Yoshida Hiroyuki H Shiokawa Masahiro M Kuwada Takeshi T Muramoto Yuya Y Ota Sakiko S Nishikawa Yoshihiro Y Maeda Hirona H Kakiuchi Nobuyuki N Okamoto Kanako K Yamazaki Hajime H Yokode Masataka M Nakamura Takeharu T Matsumoto Shimpei S Hirano Tomonori T Okada Hirokazu H Marui Saiko S Sogabe Yuko Y Matsumori Tomoaki T Mima Atsushi A Uza Norimitsu N Eso Yuji Y Takai Atsushi A Takahashi Ken K Ueda Yoshihide Y Kodama Yuzo Y Chiba Tsutomu T Seno Hiroshi H

Journal of gastroenterology 20230613 8

<h4>Background</h4>Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown.<h4>Methods</h4>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 so ...[more]

PMID: 37310456

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Project description:Background & aimsBetter biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvβ6 (anti-αvβ6) autoantibodies have been described in patients with UC. We tested for the presence of anti-αvβ6 antibodies in the preclinical phase of UC and studied their association with disease-related outcomes after diagnosis.MethodsAnti-αvβ6 autoantibodies were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense preclinical cohort (PREDICTS [Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects]). In a distinct, external validation cohort (Crohn's and Colitis Canada Genetic Environmental Microbial project cohort), we tested 12 pre-UC subjects and 49 matched controls. Furthermore, anti-αvβ6 autoantibodies were measured in 2 incident UC cohorts (COMPASS [Comprehensive Care for the Recently Diagnosed IBD Patients], n = 55 and OSCCAR [Ocean State Crohn's and Colitis Area Registry], n = 104) and associations between anti-αvβ6 autoantibodies and UC-related outcomes were defined using Cox proportional hazards model.ResultsAnti-αvβ6 autoantibodies were significantly higher among individuals who developed UC compared with controls up to 10 years before diagnosis in PREDICTS. The anti-αvβ6 autoantibody seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 time points. Anti-αvβ6 autoantibodies predicted UC development with an area under the curve of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvβ6 autoantibodies in preclinical UC samples was validated in the GEM cohort. Finally, high anti-αvβ6 autoantibodies was associated with a composite of adverse UC outcomes, including hospitalization, disease extension, colectomy, systemic steroid use, and/or escalation to biologic therapy in recently diagnosed UC.ConclusionsAnti-integrin αvβ6 autoantibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.

Dataset Information

Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis.

Background

Methods

Results

Conclusions

Publications

Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis.

Similar Datasets

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