scholarly journals P165 Non-invasive biomarkers of type III collagen cross-linking reflects fibrolysis in patient with luminal CROHN’S DISEASE

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S241-S242
Author(s):  
M Pehrsson ◽  
L E Godskesen ◽  
A C Bay-Jensen ◽  
M Asser Karsdal ◽  
A Krag ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Disease Activity ◽  
Collagen Degradation ◽  
Inactive Disease ◽  
Type Iii Collagen ◽  
Collagen Formation ◽  
Type Iii ◽  
Ctx Iii ◽  
Collagen Remodelling ◽  
Active Disease

Abstract Background Type III collagen of the interstitial matrix is highly expressed in fibrotic tissue of Crohn’s disease (CD) and suggested to undergo remodelling during the characteristic deep tissue inflammation. Periods of inflammatory flares and remission could thus be reflected by varying degrees of type III collagen degradation and formation in relation to fibrogenesis and resolution of fibrosis. The aim was to investigate the association between type III collagen remodelling and CD disease phenotypes based on the Montreal classification Methods 40 CD patients were endoscopically assessed according to the Montreal B classification (luminal or stricturing phenotype) and Harvey Bradshaw Index for clinical disease activity (<4 = inactive; >4 = active). Patients were stratified based on both the Montreal B classification and HBI scores. Biomarkers were assessed by ELISA: 1) CTX-III (cross-linked protease degraded fragments of type III collagen), PC3X (cross-linked type III collagen formation), 3) PRO-C3 (type III collagen formation), and 4) C3M (MMP-9 degradation fragments) Results Biomarker levels of CTX-III was significantly elevated in CD patients with luminal- and clinically inactive- disease compared to patients with stricturing- and clinically inactive- disease and luminal- and clinically active- disease (p<0.01 and p<0.05, fig 1A). The levels of net fibrolysis of cross-linked type III collagen (CTX-III/PC3X) was significantly higher in patients with luminal- and clinically inactive- disease compared to patients with stricturing- and clinically inactive- disease (p<0.001), luminal- and clinically active- disease (p<0.001), and patients with stricturing- and clinically active- disease (p<0.05, fig 1C). Significantly elevated levels of net type III collagen degradation (C3M/PRO-C3) were observed in patients with a luminal- and clinically active- disease compared to luminal- and clinically inactive- as well as stricturing- and clinically inactive- disease (p<0.05). Furthermore, net type III collagen degradation was elevated compared to patients with stricturing- and clinically active- disease (p<0.05, fig 1F). Biomarker levels of PC3X, C3M, and PRO-C3 were unable to differentiate between patient groupings (fig 1B, D, and E) Conclusion Proteolytic degradation of cross-linked type III collagen (CTX-III) reflecting resolution of fibrosis in CD patients with luminal disease, may be associated with a protective effect against fibrogenesis and progression to fibrostenosis. These data indicate differences in cross-linked and non-cross-linked type III collagen remodelling in CD patients, and their potential use for differentiating patient phenotypes and disease activity

scholarly journals P047 Differences in extra cellular matrix remodelling in highly active Crohn’s disease and ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S156-S157
Author(s):  
V Domislović ◽  
J H Mortensen ◽  
M A Karsdal ◽  
M Brinar ◽  
T Manon-Jensen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Type Iv Collagen ◽  
Collagen Degradation ◽  
Type Iii Collagen ◽  
Collagen Turnover ◽  
Collagen Formation ◽  
Type Iii ◽  
Highly Active ◽  
Type Iv

Abstract Background Ulcerative colitis (UC) and Crohn’s disease (CD) require continuous evaluation of disease activity and response to therapy. Current gold standard is endoscopy; therefore it is important to investigate biomarkers associated with endoscopic disease activity. Extra cellular matrix (ECM) consists of basement membrane (BM) and interstitial matrix (IM). BM consists mainly of type IV collagen, while IM of types I, III and V collagen. Pathological environment leads to impaired remodelling, structure, quality and function of the ECM. We investigated biomarkers of collagen degradation and formation and their association with endoscopic disease activity and in patients with CD and UC. Methods In this cross-sectional study, we measured six biomarkers of ECM remodelling in 94 IBD patients (60 with CD and 34 UC). Biomarkers of type III collagen degradation (C3M) and formation (PRO-C3), type IV collagen degradation (C4M), formation (PRO-C4), type V collagen formation (PRO-C5) and PROC23 were measured in serum by ELISA. Inflammatory activity was measured using endoscopic scores; SES-CD for CD, MES and modified MES (mMES) for UC. Patients were divided in remission and mild activity group vs. moderate-to-severe activity (SES-CD < 3 vs. ≥3 and MES < 2 vs. ≥2) Student t-test and correlation analysis were applied in statistical analysis. Results CD patients with moderate and severe disease had lower levels of PRO-C3 (14.7 ± 10.5 vs. 9.9 ± 4.6, p = 0.04), and higher levels of C4M (26.54 ± 10.5 vs. 37.8 ± 20, p = 0.009) compared with patients in remission and mild disease. Biomarker of type III collagen turnover (C3M/PROC3) showed higher levels in moderate and severe active disease in CD (1 ± 0.5 vs. 1.8 ± 1.1, p = 0.006). UC patients with moderate to severe activity showed higher levels of type III collagen turnover biomarker (C3M/PROC3) (1.1 ± 0.4 vs. 1.97 ± 1, p = 0.049). C4M correlated positively (r = 0.28, p = 0.03) and PRO-C3 correlated negatively (r = −0.29, p = 0.03) to SES-CD and combined in a multivariate regression model (r = 0.39, p = 0.009). C3M (r = 0.60, p = 0.004) and C4M (r = 0.36, p = 0.039) correlated positively with mMES. Conclusion In highly active CD, there is increased type IV collagen degradation and reduced type III collagen formation. Both biomarkers significantly correlate with SES-CD, with increased correlation when combined together. Type III collagen turnover is increased in highly active CD and UC. Biomarkers of types III and IV collagen degradation correlate significantly with mMES. Biomarkers of types III and IV collagen could be used to differentiate highly active CD from UC. Our findings suggest that biomarkers of basement membrane and interstitial matrix remodelling may be used as surrogate markers for monitoring of disease activity for UC and CD.

scholarly journals The Role of Bowel Ultrasound in Detecting Subclinical Inflammation in Pregnant Women with Crohn’s Disease

2018 ◽  
Vol 2 (4) ◽  
pp. 153-160 ◽  
Author(s):  
Yvette Leung ◽  
Hang Hock Shim ◽  
Rune Wilkens ◽  
Divine Tanyingoh ◽  
Elnaz Ehteshami Afshar ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Pregnant Women ◽  
Inactive Disease ◽  
Subclinical Inflammation ◽  
One Year ◽  
Bowel Sonography ◽  
Bowel Ultrasound ◽  
Active Disease

Abstract Background and Aims Maintaining disease remission improves outcomes for pregnant women with Crohn’s disease (CD). As symptoms may correlate poorly with disease activity in the gravid state, we investigated the utility of bowel sonography during pregnancy to assess disease activity. Methods We conducted a prospective observational cohort study of pregnant women with CD undergoing bowel sonography between July 1, 2012, and December 1, 2016. Clinically active disease was defined using standardized clinical indices (Harvey Bradshaw Index >4 for active disease). Sonographic findings were graded as inactive (normal, mild) or active (moderate, severe) by expert radiologists. Results There were 91 pregnancies in 82 CD patients. Symptoms were present in 12 pregnancies; however, eight (67%) had sonographic findings of inactive disease, and escalation of therapy was not initiated. Conversely, sonographically active disease in seven asymptomatic pregnancies resulted in four women escalating therapy. The remaining three women declined escalation of therapy, one had a miscarriage, and the other two women had persistently active disease on sonography and endoscopy at one-year postpartum. Conclusions Bowel ultrasound may detect subclinical inflammation in asymptomatic pregnant women with CD and stratify CD activity in symptomatic patients. Therefore, bowel sonography should be considered as a useful adjunct for the assessment of the pregnant woman with Crohn’s disease.

Evaluation of Crohn’s Disease Activity: Development of an Ultrasound Score in a Multicenter Study

2020 ◽  
Vol 27 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Tomás Ripollés ◽  
Joaquín Poza ◽  
Cristina Suarez Ferrer ◽  
María J Martínez-Pérez ◽  
Ana Martín-Algíbez ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Wall Thickness ◽  
Roc Curve ◽  
Color Doppler ◽  
High Accuracy ◽  
Inactive Disease ◽  
Ultrasound Score ◽  
Active Disease

Abstract Objective Our goal in this multicentric prospective study was 2-fold: first, to test the diagnostic accuracy of ultrasound, color Doppler imaging (CDI), and contrast-enhanced ultrasound (CEUS) in identifying disease activity in patients with Crohn’s disease (CD) compared with endoscopy as the reference standard; and, second, to construct a sonographic score that allows disease activity to be detected. Materials and methods Seventy-two patients with CD from 3 hospitals underwent within a 30-day period both colonoscopy and ultrasound (US), including mural thickness, CDI, and CEUS, prospectively as part of clinical care. A multivariate analysis was carried out to assess the influence of each of the ultrasound variables in predicting endoscopic activity. We then developed a predictive ultrasound score for disease activity, and a receiver operating characteristic (ROC) curve was constructed to determine the area under the ROC curve (AUC) and the best cut-off score value to discriminate between active and inactive disease. Results Sonographic findings that were independent predictors of the presence of active disease at endoscopy were wall thickness, color grade, and contrast parameters. A score based on those variables showed high accuracy in predicting active disease, with an area under the ROC curve of 0.972. A simpler index, without contrast parameters, also showed high accuracy in detecting disease activity (AUC, 0.923). Conclusion A score based on wall thickness, color Doppler grade, and contrast parameters showed high accuracy in predicting active disease. A score without including the use of contrast agent had practically similar results and is easier to use in monitoring response to treatment.

scholarly journals FP272BIOMARKERS OF TYPE VI COLLAGEN FORMATION AND TYPE III COLLAGEN DEGRADATION CAN REFLECT RENAL FIBROSIS IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i123-i123
Author(s):  
Nadja Sparding ◽  
Federica Genovese ◽  
Morten Asser Karsdal ◽  
Veronika Satrapova ◽  
Doubravka Frausova ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Collagen Degradation ◽  
Type Iii Collagen ◽  
Type Vi Collagen ◽  
Collagen Formation ◽  
Type Iii ◽  
Anca Associated Vasculitis

scholarly journals Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease

2017 ◽  
Vol 46 (1) ◽  
pp. 26-39 ◽  
Author(s):  
W. T. van Haaften ◽  
J. H. Mortensen ◽  
M. A. Karsdal ◽  
A. C. Bay-Jensen ◽  
G. Dijkstra ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Type Iii Collagen ◽  
Collagen Formation ◽  
Type Iii

The Patient Activity Scale-II Is a Generic Indicator of Active Disease in Patients with Rheumatic Disorders

2010 ◽  
Vol 37 (9) ◽  
pp. 1932-1934 ◽  
Author(s):  
KETNA PAREKH ◽  
WILLIAM J. TAYLOR
Keyword(s):  
Disease Activity ◽  
Diagnostic Category ◽  
Treatment Decision ◽  
Disease State ◽  
Self Report ◽  
Inactive Disease ◽  
Treatment Intensity ◽  
Activity Scale ◽  
The Relationship ◽  
Active Disease

Objective.To determine whether the Patient Activity Scale-II (PAS-II) is a generic measure of disease activity by assessing whether the relationship of PAS-II with treatment decision (indicating disease activity) is invariant across disease.Methods.The Health Assessment Questionnaire-II (HAQ-II), a 10 cm visual analog scale for “pain,” and another for “patient global assessment” were recorded from 1000 consecutive patients attending rheumatology outpatient clinics. Active disease was defined as treatment intensity increased and inactive disease was defined as treatment intensity unchanged or decreased. A logistic regression analysis was conducted with active disease as the dependent variable and the predictor variables were PAS-II, diagnostic category, and the interaction between diagnostic category and PAS-II.Results.PAS-II had a weak but statistically significant association with active disease that was independent of diagnosis. An increase of 1 point in PAS-II increased the odds of being in the active disease state by 1.19 (95% CI 1.10 to 1.37). The relationship between active disease state and PAS was not affected by diagnostic category.Conclusion.PAS-II can be used as a generic self-report indicator of active disease across different rheumatic disorders, and not just in rheumatoid arthritis. The strength of the relationship with disease activity is weak and physician-derived indicators remain very important.

189 MMP Degraded Type III Collagen Is a Novel Serological Biomarker for Penetrating (Montreal B3) Crohn's Disease

2016 ◽  
Vol 150 (4) ◽  
pp. S50
Author(s):  
Wouter T. van Haaften ◽  
Joachim Høg Mortensen ◽  
Morten Asser Karsdal ◽  
Anne-Christine Bay-Jensen ◽  
Gerard Dijkstra ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Type Iii Collagen ◽  
Type Iii

Urinary neopterin in patients with systemic lupus erythematosus

1991 ◽  
Vol 37 (1) ◽  
pp. 47-50 ◽  
Author(s):  
Lakana Leohirun ◽  
Phlchal Thuvasethakul ◽  
Vasant Sumethkul ◽  
Trithar Pholcharoen ◽  
VlJitr Boonpucknavig
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Inactive Disease ◽  
Clinical Activity ◽  
High Concentration ◽  
Systemic Lupus ◽  
Neopterin Concentration ◽  
Urinary Neopterin ◽  
Active Disease

Abstract Concentrations of neopterin were measured in urine specimens from 35 patients with active and eight with inactive systemic lupus erythematosus (SLE). Compared with those of apparently healthy controls, neopterin concentrations were higher in patients with active disease (P less than 0.001) and with inactive disease (P less than 0.01), those in patients with active disease being significantly higher than those in patients with inactive disease (P less than 0.001). The correlation between the neopterin concentration and evidence of disease activity was good. All of the patients with clinically active SLE had increased neopterin, but for only 37.5% (three of eight) did the neopterin concentration exceed the upper normal limit during clinical remission. The increase in neopterin concentration did not correlate with clinical courses or severity of renal function. Moreover, serial determinations of neopterin in active SLE patients showed a rapid decrease of initially high concentration, paralleling a decline of clinical activity after initiation of medical therapy. Thus, urinary neopterin may be a useful marker for monitoring disease activity in SLE patients.

scholarly journals P101 Biomarkers of elastin degradation are associated with clinical and biochemically active disease in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S185-S186
Author(s):  
M Pehrsson ◽  
V Domislović ◽  
M A Karsdal ◽  
M Brinar ◽  
A Barisic ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Activity Index ◽  
Severe Disease ◽  
Matrix Metalloproteases ◽  
Assessment Tools ◽  
Cathepsin G ◽  
Elastin Degradation ◽  
Active Disease

Abstract Background In Crohn’s disease (CD), the extensive and potentially transmural inflammation results in increased activity of both matrix metalloproteases (MMPs) and serine proteases, causing a higher degree of intestinal tissue remodelling. This increased proteolytic activity could potentially cause degradation and loss of function of mechanical and functional matrix proteins, such as elastin. Therefore, we sought to investigate the association between biomarkers of elastin degradation and the disease activity in CD patients. Methods Seventy-two CD patients and 29 healthy donors (HD) were included in the study. Disease activity was determined according to the Crohn’s disease activity index score (CDAI >150) and/or a faecal calprotectin (fCALP >250). Additionally, CD patients were endoscopically assessed according to the simple endoscopic score (SES) for CD. Different protease derived biomarkers of elastin degradation: protease-3 (ELP-3), MMP-7 (ELM-7) and cathepsin-G (EL-CG) was measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) was applied for the statistical analysis. Results The levels of ELP-3 was significantly elevated in active CD when compared with the HD (p < 0.001), and inactive CD (p < 0.01). Levels of EL-G were significantly elevated when comparing active CD and HD (p < 0.05), with the same result observed for the levels of EL-CG when comparing active CD and the HD (p < 0.05). Endoscopically, ELP-3 was shown significantly elevated in moderate–to-severe CD patients when compared with the HD (p < 0.01). Conclusion In this study, measurements of the elastin degradation markers were capable of differentiating between CD patients with either a clinically active or biochemically active disease, with the biomarker levels being significantly highest in the patients with an active disease. This was also the case when assessing endoscopic disease activity, where the protease-3-derived biomarker levels were highest in patients of moderate-to-severe disease activity. As such, the data provide indications of the beneficial use of these serum biomarkers as additional disease activity assessment tools for CD patients.

scholarly journals P549 A virtual clinic enhances the quality use of anti-TNF dose intensification and rates of treatment success using a treat-to-target approach compared with standard outpatient care in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S467-S467
Author(s):  
A Srinivasan ◽  
D R van Langenberg ◽  
R Little ◽  
M P Sparrow ◽  
P De Cruz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Outpatient Care ◽  
Inactive Disease ◽  
Treat To Target ◽  
Model Of Care ◽  
Dose Intensification ◽  
Trough Levels

Abstract Background Virtual clinics (VC) represent a novel model-of-care which promote quality use of biologics and facilitate a treat-to-target (T2T) approach. We aimed to evaluate the clinical and process-driven outcomes of intensified anti-TNF therapy for secondary loss of response (SLoR) in a VC compared with standard outpatient care (SoC). Methods A retrospective multicenter, parallel observational cohort study of patients with Crohn’s disease (CD) who underwent anti-TNF dose intensification to address SLoR with up to 2-years of follow-up was undertaken. Objective assessments of disease activity and anti-TNF trough levels at SLoR then during subsequent 6-month semesters were compared longitudinally between VC and SoC groups. ‘Anti-TNF escalation success’ was the primary endpoint, defined as achieved when two consecutive 6-month semesters of objective assessment demonstrated inactive disease. Dose intensification was defined as ‘appropriate’ if there was both objective evidence of disease activity, plus anti-TNF trough levels at or below the lower limit of the therapeutic range prior to intensification. ‘Treatment escalation failure’ was defined by the occurrence of one or more of biologic switching, discontinuation or further intensification; recommencement of corticosteroids, or IBD-related surgery. Results 149 patients (69 VC vs. 80 SoC) underwent infliximab (n = 94) or adalimumab (n = 55) dose intensification with similar baseline patient, disease and treatment characteristics between cohorts. The median duration of follow-up post dose-intensification was 1.9 and 1.5 years for the SoC and VC cohorts respectively (p = 0.37). There were higher rates of appropriate dose intensification (82.6 vs. 40.0%, p < 0.01) across the VC cohort. Higher proportions of anti-TNF escalation success (60.9 v 35.0%, p < 0.01), biomarker remission (i.e., C-Reactive Protein (<5mg/l) and faecal calprotectin (<150 μg/ml) normalisation, log-rank tests, p = 0.06 and p < 0.01 respectively), tight disease monitoring (84.1 vs. 28.8%, p < 0.01) and de-escalation of intensified therapy (21.3 vs. 10.0%, p = 0.03) were also achieved by the VC cohort following dose-intensification. Conclusion This study favoured a VC-led model of care over standard outpatient-based IBD care in facilitating an effective T2T approach to CD management. A VC model of care improved quality use of intensified anti-TNF therapy through processes that promoted appropriate dose intensification and encouraged more frequent anti-TNF dose de-escalation. Moreover, tight semester-based monitoring using a T2T-based strategy facilitated by the VC was associated with improved treatment outcomes.

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