scholarly journals POS0966 IDENTIFICATION OF PATIENTS AFFECTED WITH ANKYLOSING SPONDYLITIS AND INFLAMMATORY BOWEL DISEASE OVERLAP USING COLLAGEN BIOMARKERS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 748.1-748
Author(s):  
S. Holm Nielsen ◽  
A. Stahly ◽  
E. H. Regner ◽  
A. C. Bay-Jensen ◽  
M. Karsdal ◽  
...  

Background:Chronic inflammatory arthritis is a hallmark of Ankylosing Spondylitis (AS), where co-existence of inflammatory bowel disease, such as Crohn’s Disease (CD) is prominent. The clinical overlap of AS and CD has raised the hypothesis that these conditions may have similar pathophysiological mechanisms. Both indications are characterized by an altered extracellular matrix turnover, where particularly collagens are remodeled.Objectives:We investigated the association between biomarkers of collagen degradation in healthy controls and patients with AS, CD and AS/CD overlap, with the aim to investigate the biomarkers’ ability to identify patients with AS/CD overlap.Methods:Patients with AS fulfilling ASAS criteria (n=13), biopsy-proven CD (n=14), subjects with AS and CD overlap (n=10) and healthy controls (n=11) undergoing standard of care colonoscopies were included in the study. The collagen degradation biomarkers measuring type III, IV, VI and X collagen (C3M, C4M, C6M and C10C, respectively) were measured in EDTA plasma samples from all subject groups. Biomarkers were measured by competitive ELISAs. Statistical analysis was performed using an ANCOVA adjusted for age, an AUROC analysis and spearman correlations.Results:The collagen biomarker C4M was significantly higher in patients with AS/CD overlap compared to AS, CD and HCs (all p<0.0001, Figure 1A). The blood levels of C4M in AS patients were significantly lower than HC (p=0.0003), while CD also showed a lower level compared to HC though not significant (p=0.0798). No difference was found between AS and CD alone. In an AUROC analysis, C4M showed a complete separation between the patients with AS/CD overlap compared to HC, AS and CD with an AUC=1.00; p=0.0001. No differences were found between the patient groups for C3M, C6M and C10C (Figure 1, B-D). 91.3 % of patients with AS, 92.8% of patients with CD and 60 % of patients with AS and IBD overlap were actively treated with TNF-α inhibitors, which may explain the suppression of the collagen degradation biomarker levels in AS, CD and AS/IBD overlap compared to healthy controls[1,2]. No correlations were found between the collagen biomarkers and CRP, BASDAI, SCCAI or HBI scores.Conclusion:Degradation of type IV collagen quantified by C4M showed a complete separation of patients with AS/IBD overlap, compared to AS, CD and HC patients, which indicates an excessive collagen degradation and epithelial turnover. This biomarker could potentially be used to identify patients affected by both manifestations, and guide treatment decisions.References:[1]van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, et al. Serological Biomarkers of Tissue Turnover Identify Responders to Anti-TNF Therapy in Crohn’s Disease: A Pilot Study. Clin Transl Gastroenterol. 2020;11:e00217.[2]Siebuhr AS, Bay-Jensen AC, Karsdal MA, Lories RJ, de Vlam K. CRP and a biomarker of type I collagen degradation, C1M, can differentiate anti-inflammatory treatment response in ankylosing spondylitis. Biomark Med. 2016;10:197–208.Figure 1.Levels of C4M (A), C3M (B), C6M (C) and C10C (D) in EDTA plasma from patients diagnosed with AS (n=13), CD (n=14), AS and CD overlap (n=10) and HC (n=11). Graphs are presented as Tukey box plots. Statistical significance: ****p<0.0001.Disclosure of Interests:Signe Holm Nielsen Employee of: Full time PostDoc at Nordic Bioscience and Technical University of Denmark, Andrew Stahly: None declared, Emilie H. Regner: None declared, Anne-Christine Bay-Jensen Shareholder of: Stocks at Nordic Bioscience, Employee of: Full-time employee at Nordic Bioscience, Morten Karsdal Shareholder of: Stocks at Nordic Bioscience, Employee of: Full-time employee at Nordic Bioscience, Kristine A. Kuhn: None declared.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1647.2-1647
Author(s):  
G. Lukina ◽  
P. Kulakova ◽  
N. Savenkova ◽  
E. Volnukhin ◽  
A. Kovshik ◽  
...  

Background:Аnkylosing Spondylitis (AS) is closely associated with inflammatory bowel disease (IBD). About 6-46% of patients with IBD have various lesions of the musculoskeletal system [1]. 5-10% of patients with spondylarthritis (SpA) eventually develop IBD, with Crohn’s disease (CD) being more common than Ulcerative colitis (UC) [2]. Determining the level of fecal calprotectin (FC) is a study that allows to diagnose IBD. The concentration of FC directly depends on the neutrophil infiltration of the intestinal mucosa and has a direct connection with the activity of the inflammatory process [3]. It is known that level of FC increases in 2/3 of patients with AS and is closely related to parameters reflecting higher disease activity [4].Objectives:The aim of this study was to evaluate the frequency of IBD in patients with AS using an assessment of FC level.Methods:In the analysis were included 40 patients with AS, fulfilling the modified New York criteria, among them man -26 (65%), woman -14 (35%), mean age of patients was 41.2 ±10.5, mean disease duration - 13±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: 100-1800 µg /g.Results:All patients had a high disease activity, mean BASDAI was 5.2 ± 1.7, mean ASDAS CRP 3.8 ± 1.1. 35 patients (87.5 %) had FC level more than 100 µg / g, the remaining 5 patients (12.5%) less than 100 µg /g. 12 patients (30 %) had FC level more than 1,800 µg / g, 23 (57.5 %) from 101 µg / g to 1800 µg / g. All patients with FC levels more than 100 µg / g showed an increase CRP (mean 28.4 mg / l) and ESR (mean 36.3 mm\h) levels. IBD were diagnosed in 9 cases (22.5%): 5 patients (12.5 %) with CD and 4 patients (10 %) - UC, in the remaining cases (77.5%) was no intestinal pathology.Conclusion:The results showed high frequency of IBD in patients with AS. Patients with high FC levels (more than 100 μg/g) had high disease activity (AS). In most cases, inflammatory bowel disease were diagnosed in patients with FC levels more than 100 µg/g.References:[1] Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001 Apr;96(4):1116-22.[2] Klingberg, E., Strid, H., Stahl, A.et al. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther 2017. 19(1):21[3] Cypers H, Varkas G, Beeckman S, et al. Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis. Annals of the Rheumatic Diseases. 2016. 75:1357-1362[4] Arzu Duran, Senol Kobak, Nazime Sen, et al. Fecal calprotectin is associated with disease activity in patients with ankylosing spondylitis. Bosnian Journal of Basic Medical Sciences. 2016. 16 (1):71-4Disclosure of Interests:Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Polina Kulakova: None declared, Nadezhda Savenkova: None declared, Evgeniy Volnukhin: None declared, Anton Kovshik: None declared, Elena Alexandrova: None declared, Alexandr Novikov: None declared


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Luisa Guidi ◽  
Carla Felice ◽  
Annabella Procoli ◽  
Giuseppina Bonanno ◽  
Enrica Martinelli ◽  
...  

Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factorα(TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+(Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFαtherapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3+cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFαtherapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD). No significant differences were found in LP FOXP3+cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFαmay affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Aifeng Lin ◽  
Robert D. Inman ◽  
Catherine J. Streutker ◽  
Zhenbo Zhang ◽  
Kenneth P. H. Pritzker ◽  
...  

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e041733
Author(s):  
Paul Moayyedi ◽  
Glenda MacQueen ◽  
Charles N Bernstein ◽  
Stephen Vanner ◽  
Premysl Bercik ◽  
...  

IntroductionGut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome.Methods and analysisThis 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity.Ethics and disseminationApproval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.Trial registration number:NCT03131414


2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Rebecca Lawrence ◽  
Cuckoo Choudhary

Abstract Background Psychological comorbidities are common among people with inflammatory bowel disease (IBD) and are associated with worse disease outcomes. Evidence-based psychotherapy is an effective means to increase psychosocial support. This study aimed to identify the barriers to attending psychotherapy. Methods This electronic survey study included a demographic, quality of life, and barriers to psychotherapy questionnaire. Quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Barriers were assessed using the Perceived Barriers to Psychological Treatments scale (PBPT). Linear regression was used to identify participant characteristics associated with higher PBPT scores. Results One hundred eighty-seven participants completed the study. Fifty-eight percent of participants had ≥1 significant barrier. Time (28%), knowledge about the availability of services (25%), and cost (19%) were the most common barriers. Least common were stigma (14%), lack of motivation (12%), and emotional concerns (7%). Lower SIBDQ scores, being male, not being full-time employed, having Crohn disease, and being in disease remission were associated with higher PBPT scores. Conclusions Knowledge about the availability of services, time constraints, and cost are the leading barriers to psychotherapy among people with IBD. Care providers should develop a network of psychotherapists available to those with IBD. Being male and not being full-time employed may be risk factors for greater barriers. Further research is needed on barriers among groups underrepresented in this study and on novel psychotherapy solutions, like telehealth and low-cost options.


1991 ◽  
Vol 5 (5) ◽  
pp. 167-170 ◽  
Author(s):  
Hugh J Freeman ◽  
Urs P Steinbrecher ◽  
WC Peter Kwan ◽  
Stephanie Ensworth

An 18-year-old female with ankylosing spondylitis developed fever, abdominal pain and diarrhea on two occasions after starting sulphasalazine therapy. Flexible sigmoidoscopy revealed pseudomembranous colitis; fecal cultures were positive forClostridium difficile; andC difficiletoxin assay was positive. Despite the frequent use of sulphasalazine in the management of inflammatory bowel disease, this complication has been apparently rare. Clinicians should be wary of the onset of diarrhea in patients receiving sulphasalazine, whether for inflammatory bowel disease or other conditions.


2020 ◽  
Vol 4 (s1) ◽  
pp. 92-92
Author(s):  
Matthew Ostrowski ◽  
Eric C. Martens

OBJECTIVES/GOALS: This study seeks to culture and characterize mucus-degrading microbes from the microbiome of inflammatory bowel disease (IBD) patients. METHODS/STUDY POPULATION: Stool will be collected from IBD patients and healthy first-degree relatives, then enriched for mucin-degrading microbes through growth on porcine rectal mucin. Dilution plating in both liquid and solid culture formats will be employed to isolate strains capable of growth on mucin. Cultures that are positive for mucin degradation will be identified with 16S rRNA sequencing; unique isolates will be genome sequenced and transcriptionally profiled on simple monosaccharides and mucin in order to identify putative mucin-degrading genes. The abundance of novel enzymes, pathways, and microbes will be compared in healthy and IBD patient populations using existing datasets in the literature. RESULTS/ANTICIPATED RESULTS: We expect to isolate previously uncultured mucin-degrading microbes, which will likely include new strains and possibly new species of bacteria. Through the transcriptomic characterization of mucin-degrading pathways, we will expand the lexicon of known mucin-degrading enzymes and pathways used by bacteria in the human colon. We expect mucin-degrading microbes to be more abundant and active in IBD patients compared to healthy controls. DISCUSSION/SIGNIFICANCE OF IMPACT: There is no cure for IBD and treatment relies heavily on suppressing a patient’s immune system. This research seeks to understand the contribution of the gut microbiota in the pathogenesis of IBD, which may lead to future therapeutic targets.


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