scholarly journals Oncostatin M Is a Biomarker of Diagnosis, Worse Disease Prognosis, and Therapeutic Nonresponse in Inflammatory Bowel Disease

Author(s):  
Sare Verstockt ◽  
Bram Verstockt ◽  
Kathleen Machiels ◽  
Maaike Vancamelbeke ◽  
Marc Ferrante ◽  
...  

Abstract Background Oncostatin M (OSM) has been implicated in the pathogenesis of inflammatory bowel disease (IBD) and as a marker for nonresponsiveness to anti-tumor necrosis factor (TNF) therapy. We further unraveled the potential of OSM and related receptors as markers of diagnosis, prognosis, and therapy response in IBD. Methods We collected inflamed mucosal biopsies and serum from patients with Crohn disease (CD) and with ulcerative colitis: (1) newly diagnosed patients who were treatment-naïve, (2) patients initiating anti-TNF or (3) vedolizumab therapy, (4) postoperative patients with CD, and (5) multiple-affected families with IBD including unaffected first-degree relatives (FDRs). We measured the gene expression of mucosal OSM and its receptors OSMR/LIFR and co-receptor IL6ST, and the protein expression of serum OSM. Statistical significance was defined as P < 0.05. Results Newly diagnosed patients showed significantly increased mucosal OSM/OSMR compared with control patients, with the highest enrichment for OSM (fold change [FC] >17.9). Likewise, ileal OSM/OSMR were significantly upregulated in postoperative recurrent CD. Serum OSM was increased in newly diagnosed patients and postoperative patients with recurrent CD (FC ≥ 2.6). In families with IBD, higher serum levels were observed in FDRs than in control families (FC = 2.2). Furthermore, elevated colonic OSM/OSMR (but not serum OSM) were associated with the early need for biologic therapy (FC ≥ 1.9), and higher OSM was also predictive of primary nonresponse to both anti-TNF and vedolizumab therapy (FC ≥ 2.4). Immunohistochemistry highlighted mucosal OSM expression in macrophages. Conclusions We found that OSM is a diagnostic biomarker in the tissue and serum not only of newly diagnosed patients with IBD and postoperative patients with recurrent CD but also of their FDRs. Higher colonic OSM levels are furthermore associated with poor prognosis and with primary nonresponse to biologic therapies. Therefore, OSM could guide clinical decision-making.

2021 ◽  
Vol 11 (11) ◽  
pp. 1130
Author(s):  
Laura A. Lucaciu ◽  
Maria Ilieș ◽  
Ștefan C. Vesa ◽  
Radu Seicean ◽  
Shahida Din ◽  
...  

Interleukin (IL)-17 and IL-23 are crucial for mediating gut mucosal inflammation in inflammatory bowel disease (IBD), which has led to new therapeutic strategies. We assessed the relevancy of IL-17 and IL-23 serum levels as potential biomarkers towards severe IBD discrimination and disease-related complications. Sixty-two patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) were included. Serum IL-17 and IL-23 were measured by sandwich enzyme-linked immunosorbent assays (ELISA). IL-23 and fecal calprotectin (FCal) were significantly higher in severe CD (p < 0.001) and UC (p < 0.001 and p = 0.001, respectively), compared to mild or moderate. Elevated C-reactive protein (CRP) was correlated with severe disease only in CD (p = 0.008), whereas for UC, disease severity was associated with increased IL-17 values (p < 0.001). Diagnostic role of IL-23 was superior to FCal in discriminating between severe and mild to moderate CD (p < 0.001). IL-23 levels were also significantly higher in CD patients with intestinal complications (p = 0.04). Both IL-17 and IL-23 correlate with IBD severity, and IL-23 might be a promising novel biomarker for severe CD. Identifying the dominant IL pathway involved in IBD severity could serve as guidance for clinical decision-making on biologic therapy.


2021 ◽  
Vol 14 ◽  
pp. 175628482098819
Author(s):  
Klaudia Farkas ◽  
Daniella Pigniczki ◽  
Mariann Rutka ◽  
Kata Judit Szántó ◽  
Tamás Resál ◽  
...  

The coronavirus disease 2019 (COVID-19) outbreak emerged in December 2019 in China and rapidly spread worldwide. Inflammatory bowel disease (IBD) patients are likely to be more susceptible to viral infections, and this is significantly influenced by the type of therapy they receive. Thus, issues specifically concerning the medical treatment of IBD patients were shortly addressed at the beginning of the pandemic. However, recently available data on the occurrence and outcome of SARS-CoV-2 infection in IBD patients does not address the concerns raised at the beginning of the pandemic. Growing evidence and the rapid changes happening over the past few weeks have helped elucidate the current situation, contribute to our understanding of the disease, and many previously raised questions could now be answered. We hereby summarise available evidence regarding viral infections and IBD, focusing on SARS-CoV infections, and we provide practical recommendations related to patient management during the COVID-19 pandemic era.


2021 ◽  
Author(s):  
Archana Shubhakar ◽  
Bas C Jansen ◽  
Alex T. Adams ◽  
Karli R. Reiding ◽  
Nicholas T. Ventham ◽  
...  

Abstract A blood-based prognostic biomarker to guide clinical decision-making at diagnosis of inflammatory bowel disease (IBD) would be immensely helpful. We investigated a composite serum N-glycomic biomarker to predict future disease course in 244 newly diagnosed IBD patients. Forty-seven individual glycan peaks were analysed using ultra-high performance liquid chromatography identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio (HR) 25.9, p = 1.1×10− 12; 95% confidence interval (CI), 8.52–78.78). Application to an independent replication cohort of 54 IBD patients yielded a HR of 5.1 (p = 1.1×10− 5; 95% CI, 2.54–10.1). These data demonstrate the predictive capacity of serum N-glycan biomarkers and represent a step towards personalized medicine in IBD.


2018 ◽  
Vol 11 ◽  
pp. 1756283X1774473 ◽  
Author(s):  
Yannick Derwa ◽  
Christopher J.M. Williams ◽  
Ruchit Sood ◽  
Saqib Mumtaz ◽  
M. Hassan Bholah ◽  
...  

Objectives: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. Methods: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare and faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. Results: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84–17.0] and UC (OR 10.8; 95% CI 1.8–64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49–5.39; and OR 0.21; 95% CI 0.21–1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84–34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46–6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47–43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28–14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. Conclusions: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.


Author(s):  
Matthijs Oyaert ◽  
An Boel ◽  
Julie Jacobs ◽  
Stefanie Van den Bremt ◽  
Maxime De Sloovere ◽  
...  

AbstractBackground:We evaluated the analytical performance of six different faecal calprotectin immunoassays together with their diagnostic accuracy in the discrimination between functional and organic bowel disorders.Methods:The faecal samples were obtained from inflammatory bowel disease patients (n=27) at the time of diagnosis [Crohn’s disease (n=15), colitis ulcerosa (n=12)], gastroenterologic disease control patients (n=52) and rheumatologic disease control patients (n=26). All individuals included in the study underwent a concurrent ileocolonoscopy. Analytical performance (imprecision, accuracy, carry-over, correlation and agreement) and diagnostic accuracy (sensitivity, specificity, likelihood ratios) of the different assays were evaluated.Results:All methods demonstrated good analytical performance, but within-run and total imprecision varied depending on the assay methodology used. Using Passing Bablok and Bland-Altman analyses, low quantitative agreement was observed between the assays. All assays showed excellent diagnostic accuracy, with areas under the receiver operating characteristic curves (ROC) ranging from 0.974 to 0.998. The AUCs were not significantly different between assays (p>0.05). Diagnostic sensitivity at the cut-off at a fixed specificity of 75% ranged from 95.2% to 100%. Introduction of multiple result intervals increased the clinical interpretation of all the assays.Conclusions:Analytical and diagnostic performance of the evaluated faecal calprotectin assays is good, but numerical values differ substantially between the assays necessitating the use of different clinical cut-offs. Introduction of multiple result intervals aids in clinical decision-making.


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