scholarly journals Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sanam Soomro ◽  
Suresh Venkateswaran ◽  
Kamala Vanarsa ◽  
Marwa Kharboutli ◽  
Malavika Nidhi ◽  
...  

AbstractIn the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

2019 ◽  
Vol 25 (12) ◽  
pp. 1945-1956 ◽  
Author(s):  
Gertrude van den Brink ◽  
Luuk Stapersma ◽  
Anna Sophia Bom ◽  
Dimitris Rizopolous ◽  
C Janneke van der Woude ◽  
...  

Abstract Background Anxiety and depressive symptoms are prevalent in patients with inflammatory bowel disease (IBD) and may negatively influence disease course. Disease activity could be affected positively by treatment of psychological symptoms. We investigated the effect of cognitive behavioral therapy (CBT) on clinical disease course in 10–25-year-old IBD patients experiencing subclinical anxiety and/or depression. Methods In this multicenter parallel group randomized controlled trial, IBD patients were randomized to disease-specific CBT in addition to standard medical care (CBT + care us usual [CAU]) or CAU only. The primary outcome was time to first relapse in the first 12 months. Secondary outcomes were clinical disease activity, fecal calprotectin, and C-reactive protein (CRP). Survival analyses and linear mixed models were performed to compare groups. Results Seventy patients were randomized (CBT+CAU = 37, CAU = 33), with a mean age of 18.3 years (±50% < 18 y, 31.4% male, 51.4% Crohn’s disease, 93% in remission). Time to first relapse did not differ between patients in the CBT+CAU group vs the CAU group (n = 65, P = 0.915). Furthermore, clinical disease activity, fecal calprotectin, and CRP did not significantly change over time between/within both groups. Exploratory analyses in 10–18-year-old patients showed a 9% increase per month of fecal calprotectin and a 7% increase per month of serum CRP in the CAU group, which was not seen in the CAU+CBT group. Conclusions CBT did not influence time to relapse in young IBD patients with subclinical anxiety and/or depression. However, exploratory analyses may suggest a beneficial effect of CBT on inflammatory markers in children.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255974
Author(s):  
Jong-Mi Lee ◽  
Joo Hee Jang ◽  
Ji Hyeong Ryu ◽  
Jaeeun Yoo ◽  
Bo-In Lee ◽  
...  

Background Fecal calprotectin (FC) is widely used for the diagnosis and monitoring disease activity of inflammatory bowel disease (IBD). Quantitative rapid assays can be a reliable alternative to the time-consuming assay. This study aimed to evaluate and compare the diagnostic performance of two quantitative rapid FC assays (Ichroma calprotectin, and Buhlmann Quantum blue). Methods A total of 192 patients were included in this study; 84 patients with IBD (67 ulcerative colitis and 17 Crohn’s disease) and 108 patients with non-IBD. We compared quantitative FC levels in different disease statuses and evaluated the correlation between the FC results of the two FC kits. Diagnostic performances in predicting active IBD were evaluated in reference to different cut-off levels. Results The FC levels in 45 patients with active IBD as defined by endoscopic score were significantly higher compared to the inactive IBD and other diseases (P<0.05). Although the two assays’ results correlated (r = 0.642, P < 0.001), a significant deviation was observed (y (Buhlmannn) = -45.2 +8.9X (Ichroma)). The Diagnostic performances in predicting active IBD were comparable as area under the curve (AUC), 0.812, cut-off, 50, sensitivity, 64.4%, and specificity, 85.0% for iChroma assay and AUC, 0.826, cut-off, 100, sensitivity, 84.4%, and specificity 61.9% for Buhlmann Quantum Blue assay. FC levels using a cut-off of > 250 μg/g confirmed 85.7% (iChroma) and 64.1% (Buhlmann) of active IBD patients. Conclusion The results of the two rapid FC assays iChroma and Buhlmann showed a significant correlation, but the two test results were not interchangeable. With optimized cut-off values, rapid FC tests could be helpful in the diagnosis of IBD and differentiating active IBD from inactive or organic bowel disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eriko Yasutomi ◽  
Toshihiro Inokuchi ◽  
Sakiko Hiraoka ◽  
Kensuke Takei ◽  
Shoko Igawa ◽  
...  

AbstractLeucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn’s disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.


Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 367 ◽  
Author(s):  
Małgorzata Krzystek-Korpacka ◽  
Radosław Kempiński ◽  
Mariusz Bromke ◽  
Katarzyna Neubauer

Mucosal healing (MH) is the key therapeutic target of inflammatory bowel disease (IBD). The evaluation of MH remains challenging, with endoscopy being the golden standard. We performed a comprehensive overview of the performance of fecal-, serum-, and urine-based biochemical markers in colonic IBD to find out whether we are ready to replace endoscopy with a non-invasive but equally accurate instrument. A Pubmed, Web of Knowledge, and Scopus search of original articles as potential MH markers in adults, published between January 2009 and March 2020, was conducted. Finally, 84 eligible studies were identified. The most frequently studied fecal marker was calprotectin (44 studies), with areas under the curves (AUCs) ranging from 0.70 to 0.99 in ulcerative colitis (UC) and from 0.70 to 0.94 in Crohn`s disease (CD), followed by lactoferrin (4 studies), matrix metalloproteinase-9 (3 studies), and lipocalin-2 (3 studies). The most frequently studied serum marker was C-reactive protein (30 studies), with AUCs ranging from 0.60 to 0.96 in UC and from 0.64 to 0.93 in CD. Fecal calprotectin is an accurate MH marker in IBD in adults; however, it cannot replace endoscopy and the application of calprotectin is hampered by the lack of standardization concerning the cut-off value. Other markers are either not sufficiently accurate or have not been studied extensively enough.


2018 ◽  
Vol 11 ◽  
pp. 175628481875993 ◽  
Author(s):  
Arne Carlsen ◽  
Roald Omdal ◽  
Kristian Øgreid Leitao ◽  
Kjetil Isaksen ◽  
Anne Kristine Hetta ◽  
...  

Background: Low anti-tumor necrosis factor α (TNFα) serum concentrations may result in lack of treatment response in patients with inflammatory bowel disease. We determined the anti-TNFα drug concentrations in patients with inflammatory bowel disease and investigated whether or not subtherapeutic drug concentrations were associated with increased levels of disease activity. Methods: In a single-center cross-sectional study, we included patients with ulcerative colitis or Crohn’s disease who were receiving infliximab or adalimumab maintenance therapy. Demographic data, disease activity symptom scores (Partial Mayo Score, Harvey Bradshaw Index), inflammatory markers [C-reactive protein (CRP), fecal calprotectin], antidrug antibodies and serum drug concentrations were recorded. Therapeutic drug concentrations were defined as 3–8 mg/liter for infliximab and 5–12 mg/liter for adalimumab. Results: Of 210 patients included, 137 (65.2%) had Crohn’s disease. In the adalimumab group, subtherapeutic drug concentrations were measured in 16.7% of patients with ulcerative colitis and in 27.7% of patients with Crohn’s disease. In the infliximab group, subtherapeutic drug concentrations were found in 23% (ulcerative colitis) and 30.3% (Crohn’s disease) of patients. In Crohn’s disease, subtherapeutic adalimumab concentrations were associated with higher fecal calprotectin and CRP concentrations compared with therapeutic concentrations. Subtherapeutic infliximab concentrations in patients with Crohn’s disease were also associated with higher CRP concentrations compared with therapeutic concentrations. Conclusions: The prevalence of subtherapeutic drug levels ranged from 17% to 30%. In patients with Crohn’s disease, subtherapeutic serum drug concentrations were associated with significantly higher disease activity with both anti-TNFα agents. These findings were not observed in patients with ulcerative colitis. Clinicaltrials.gov identifier [NCT02134054]


Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 237 ◽  
Author(s):  
Andreas Munk Petersen ◽  
Hengameh Chloé Mirsepasi-Lauridsen ◽  
Marianne K. Vester-Andersen ◽  
Nikolaj Sørensen ◽  
Karen Angeliki Krogfelt ◽  
...  

Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.


Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2323
Author(s):  
Gonzalo Hijos-Mallada ◽  
Raul Velamazán ◽  
Raúl Marti ◽  
Eduardo Chueca ◽  
Samantha Arechavaleta ◽  
...  

Background: Monitoring inflammatory bowel disease patients may be challenging. Fecal calprotectin is one of the most performed tests. Other fecal biomarkers are less used in clinical practice. Rapid fecal tests that could be performed by patients may be a useful strategy to closely monitor disease activity. Methods: We performed a prospective observational study including consecutive inflammatory bowel disease patients referred for colonoscopy in a single center. Certest FOB + Transferrin + Calprotectin + Lactoferrin® (Certest Biotec S.L, Zaragoza, Spain), a one-step point-of-care test which simultaneously detects these four biomarkers was performed. Endoscopic inflammatory activity was defined using the Mayo score (≥1) in ulcerative colitis, SES-CD (>3) and Rutgeerts scores (≥1) for Crohn’s disease. Results: Out of a total of 106 patients (56.5% female, mean age 51 years), 54 (50.9%) were diagnosed with ulcerative colitis and 52 (49.1%) with Crohn’s disease. Endoscopic activity was detected in 42 patients (39.0%). Fecal calprotectin provided the best sensitivity (97.6%), with limited specificity (34.4%). Compared to calprotectin, the other 3 fecal biomarkers showed better specificity (87.5–92.1%) and lower sensitivity (45.2–59.5%). Patients with a negative result in all biomarkers (19/106—17.9%) had 100% (CI 95% 97.4–100) negative predictive value, while patients with the 4 biomarkers positive (13/106—12.3%) had 100% (CI 95% 96.1–100) positive predictive value of endoscopic inflammatory activity. AUROC of this 4 biomarker point-of-care test was 0.845 (95% CI 0.771–0.920), significantly higher than the AUROCs of any of the 4 biomarkers. Conclusions: This test may be a useful strategy to monitor inflammatory activity in clinical practice by excluding or prioritizing patients in need of a colonoscopy.


2020 ◽  
Vol 2 (37) ◽  
pp. 12-15
Author(s):  
G. V. Lukina ◽  
P. I. Kulakova ◽  
A. A. Novikov ◽  
N. A. Savenkova ◽  
E. A. Alexandrova ◽  
...  

Background. Аnkylosing spondylitis (AS) is closely associated with inflammatory bowel disease (IBD). 5–10 % of patients with SpA eventually develop inflammatory bowel disease, with Crohn's disease being more common than ulcerative colitis. Colonoscopy is usually used to diagnose inflammatory bowel disease, but this procedure is invasive. FC is clinically used to detect IBD and correlates well with clinical, endoscopic, and histological indicators of disease activity in IBD.The aim. To evaluate the incidence of inflammatory bowel disease in patients with ankylosing spondylitis.Materials and methods. In the analysis were included 40 patients with ankylosing spondylitis, among them 26 (65.0 %) men, and 14 (35.0 %) women, the average age of patients was 41.2 ± 10.5, the duration of the disease was on average 13.0 ± 8.8 years. All patients were examined with ESR, CRP, esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the fecal calprotectin levels using the method of lateral immunochromatography with the BUHLMANN Quantum Blue rapid test. Standart range: 100–1,800 µg/g.Results. All patients had a high disease activity, the average BASDAI was 5.2 ± 1.7, the average ASDAS CRP 3.8 ± 1.1. 35 (87.5 %) patients had calprotectin level more than 100 µg/g, the remaining 5 (12.5 %) patients less than 100 µg/g. 12 (30.0 %) patients had the calprotectin level more than 1,800 µg/g, 23 (57.5 %) from 101 to 1800 µg/g. All patients with FC levels more than 100 µg/g showed an increase CRP level (mean 28.4 mg/l) and ESR (mean 36.3 mm/h). IBD were diagnosed in 9 (22.5 %) cases: 5 (12.5 %) patients with Crohn's disease and 4 (10 %) patients with ulcerative colitis, in the remaining (77.5 %) cases there was no intestinal pathology.Conclusion. The results showed high frequency of IBD in patients with AS. Patients with high fecal calprotectin levels (more than 100 μg/g) had high disease activity (AS). In most cases, inflammatory bowel disease were diagnosed in patients AS with fecal calprotectin levels more than 100 µg/g.


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