Diagnostic value of anti-integrin αvβ6 antibodies in ulcerative colitis

Marafini, Irene; Laudisi, Federica; Salvatori, Silvia; Lavigna, Diletta; Venuto, Chiara; Giannarelli, Diana; Monteleone, Giovanni

doi:10.1016/j.dld.2023.06.024

Cited by 7 publications

(2 citation statements)

References 33 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: 96%

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: 96%

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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“…Recently, several publications have highlighted the presence of autoantibodies against a v b 6 in patients with ulcerative colitis [23][24][25]. Given the overlap of PSC and ulcerative colitis and that patients with PSC have autoantibodies against biliary epithelial cells [26,27], it is not surprising that a recent paper also identified a v b 6 autoantibodies in plasma from patients with PSC [28 && ].…”

Section: Key Pointsmentioning

confidence: 99%

Integrins in biliary injury and fibrosis

Schaub,

Chen,

Turner

2024

Current Opinion in Gastroenterology

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Purpose of review Current treatment options for cholangiopathies are severely limited and there is thus a critical need to identify and develop therapies. This review discusses the role of integrins in biliary injury and fibrosis and their potential as therapeutic targets. Recent findings There are a diverse set of roles that integrins play in biliary injury and fibrosis. Some integrins activate TGF-β signaling or are involved in sensing of the extracellular matrix, making them attractive targets for biliary fibrosis. In recent work, autoantibodies to αvβ6 were identified in patients with PSC, supporting the relevance of this integrin in the disease. In addition, a role for α2β1 in cyst formation was identified in a mouse model of polycystic liver disease. Leukocyte integrins (e.g. αEβ7 and α4β7) contribute to lymphocyte trafficking, making them potential targets for biliary inflammation; however, this has not yet translated to the clinic. Summary While all members of the same family of proteins, integrins have diverse roles in the pathogenesis of biliary disease. Targeting one or multiple of these integrins may slow or halt the progression of biliary injury and fibrosis by simultaneously impacting different pathologic cells and processes.

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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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Diagnostic value of anti-integrin αvβ6 antibodies in ulcerative colitis

Cited by 7 publications

References 33 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

Integrins in biliary injury and fibrosis

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

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