Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis

Yoshida, Hiroyuki; Shiokawa, M.; Kuwada, Takeshi; Muramoto, Yuya; Ota, Sakiko; Nishikawa, Yoshihiro; Maeda, Hatsuo; Kakiuchi, Nobuyuki; Okamoto, K; Yamazaki, Hajime; Yokode, Masayuki; Nakamura, Toshiyasu; Matsumoto, Shimpei; Hirano, Toshio; Okada, Hirokazu; Marui, Saiko; Sogabe, Yuko; Matsumori, Tomoaki; Mima, Atsushi; Uza, Norimitsu; Eso, Yuji; Takai, Atsushi; Takahashi, Ken; Ueda, Yoshihide; Kodama, Yuzo; Chiba, Tsutomu; Seno, Hiroshi

doi:10.1007/s00535-023-02006-6

Cited by 9 publications

(1 citation statement)

References 31 publications

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“…In addition to the biomarkers indicated above, most recently, IgG to integrin αvβ6 has been reported to be mostly found in UC compared to CD [22][23][24][25][26]. In the training and validation groups, 103/112 (92.0%) patients with UC and only 8/155 (5.2%) controls had anti-integrin αvβ6 antibodies (p < 0.001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing UC.…”

Section: Discussionmentioning

confidence: 97%

Clinical Validity of Anti-Proteinase 3 Antibodies in Patients with Inflammatory Bowel Disease: A Short Meta-Analysis

Andalucía,

Martínez-Prat,

Bentow

et al. 2023

Diagnostics

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Anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3 (PR3) represent highly established markers for patients with ANCA-associated vasculitis (AAV). PR3-ANCA have also demonstrated utility in the management of inflammatory bowel disease (IBD). More specifically, PR3-ANCA discriminate individuals with ulcerative colitis (UC) from Crohn’s disease (CD) patients and are associated with disease severity, activity, and treatment non-response. Here, we aim to summarize the current data on the diagnostic utility of PR3-ANCA in IBD. A structured, systematic literature review, including three electronic databases, was conducted on June 6th, 2023, to identify studies assessing the diagnostic accuracy of the QUANTA Flash® PR3 assay in UC vs. CD patients. Electronic searches were supplemented by hand searching. A hierarchical, bivariate, mixed-effect meta-analysis was conducted using the metandi function, as per the Cochrane collaboration recommendations. Study quality was assessed using the QUADAS-2 tool, which considers the risk of bias and applicability. Six out of a hundred and eleven citations met the inclusion criteria and reported QUANTA Flash® PR3 diagnostic accuracy in UC vs. CD (UC, n = 667, CD, n = 682 patients). The sensitivity/specificity point estimate for UC was 34.9%/95.9%. This resulted in a Diagnostic Odds Ratio (DOR) of 12.6. The risk of bias was low in the index test and reference standard domains. Four of the six studies (67%) showed an unclear risk of bias in patient selection and in flow and timing domains. All studies had low concerns about applicability in all the domains. PR3-ANCA measured with the QUANTA Flash® PR3 assay represent novel diagnostic markers in IBD and enables discrimination between UC and CD.

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Section: Discussionmentioning

confidence: 97%

Clinical Validity of Anti-Proteinase 3 Antibodies in Patients with Inflammatory Bowel Disease: A Short Meta-Analysis

Andalucía,

Martínez-Prat,

Bentow

et al. 2023

Diagnostics

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Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study

Yasuda,

Shiokawa,

Kuwada

et al. 2024

J Gastroenterol

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Background Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities. Methods Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA. Results Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn’s disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001). Conclusions We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.

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Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study

Okabe,

Yamamoto,

Shiokawa

et al. 2024

J Gastroenterol

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Background A serum biomarker for diagnosing ulcerative colitis (UC) remains to be established. Although we recently reported an anti-integrin αvβ6 antibody (V6 Ab) for diagnosing UC with high sensitivity and specificity, no large-scale validation study exists. This study aimed to validate the diagnostic value of V6 Ab for UC using a nationwide multicenter cohort study. Methods We measured V6 Ab titers in patients definitively diagnosed with UC, Crohn’s disease (CD), or other gastrointestinal disorders (OGDs). The primary outcome was the diagnostic value of V6 Ab. Secondary outcomes were factors associated with false-negative results in patients with UC and false-positive results in patients without UC and the heterogeneity of the diagnostic value of V6 Ab among the participating facilities. Results We enrolled 1241, 796, and 206 patients with UC, CD, and OGD, respectively, from 28 Japanese high-volume referral centers. The diagnostic sensitivity of V6 Ab for UC was 87.7%, and its specificities for CD and OGDs were 82.0% and 87.4%, respectively. Multivariable logistic regression analysis showed that false-negative results were associated with older age at the time of sample collection, current smokers, lower partial Mayo score, and not receiving advanced therapies in patients with UC, and false-positive results were associated with colonic CD in patients with CD. No factor was associated with false-positive results in patients with OGDs. There were no significant differences in the diagnostic value of V6 Ab among the centers. Conclusions The diagnostic value of V6 Ab for UC was validated in the large-scale nationwide multicenter study.

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Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis

Cited by 9 publications

References 31 publications

Clinical Validity of Anti-Proteinase 3 Antibodies in Patients with Inflammatory Bowel Disease: A Short Meta-Analysis

Clinical Validity of Anti-Proteinase 3 Antibodies in Patients with Inflammatory Bowel Disease: A Short Meta-Analysis

Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study

Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study

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