Serum Analyte Profiles Associated With Crohn’s Disease and Disease Location

2021 ◽  
Author(s):  
Gabrielle Boucher ◽  
Alexandre Paradis ◽  
Geneviève Chabot-Roy ◽  
Lise Coderre ◽  
Erin E Hillhouse ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Cell Types ◽  
Colorectal Disease ◽  
Serum Samples ◽  
Biological Difference ◽  
Clinical Observations ◽  
Inflammatory Processes ◽  
Multiple Cell ◽  
Disease Location

Abstract Background Crohn’s disease (CD) can affect any segment of the digestive tract but is most often localized in the ileal, ileocolonic, and colorectal regions of the intestines. It is believed that the chronic inflammation in CD is a result of an imbalance between the epithelial barrier, the immune system, and the intestinal microbiota. The aim of the study was to identify circulating markers associated with CD and/or disease location in CD patients. Methods We tested 49 cytokines, chemokines, and growth factors in serum samples from 300 patients with CD and 300 controls. After quality control, analyte levels were tested for association with CD and disease location. Results We identified 13 analytes that were higher in CD patients relative to healthy controls and that remained significant after conservative Bonferroni correction (P < 0.0015). In particular, CXCL9, CXCL1, and interleukin IL-6 had the greatest effect and were highly significant (P < 5 × 10–7). We also identified 9 analytes that were associated with disease location, with VEGF, IL-12p70, and IL-6 being elevated in patients with colorectal disease (P < 3 × 10–4). Conclusions Multiple serum analytes are elevated in CD. These implicate the involvement of multiple cell types from the immune, epithelial, and endothelial systems, suggesting that circulating analytes reflect the inflammatory processes that are ongoing within the gut. Moreover, the identification of distinct profiles according to disease location supports the existence of a biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.

scholarly journals Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 449 ◽  
Author(s):  
Yunjia Lai ◽  
Jingchuan Xue ◽  
Chih-Wei Liu ◽  
Bei Gao ◽  
Liang Chi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
High Resolution Mass Spectrometry ◽  
Signaling Cascades ◽  
Compound Identification ◽  
Serum Samples ◽  
Therapy Assessment ◽  
Integral Role ◽  
Important Pathway ◽  
Biomarker Research

: Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn’s disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn’s from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn’s disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD.

scholarly journals Fistula-Related Cancer in Crohn’s Disease: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1445
Author(s):  
Andromachi Kotsafti ◽  
Melania Scarpa ◽  
Imerio Angriman ◽  
Ignazio Castagliuolo ◽  
Antonino Caruso
Keyword(s):  
Systematic Review ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Hpv Vaccination ◽  
Perianal Fistula ◽  
Hpv Infection ◽  
Poor Quality ◽  
Colorectal Disease ◽  
Small Series ◽  
Chron's Disease

Perianal fistulizing Crohn’s disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn’s disease are also at risk of perianal fistula-related squamous cell carcinoma (SCC). Cancer arising at the site of a chronic perianal fistula is rare in patients with Crohn’s disease and there is a paucity of data regarding its incidence, diagnosis and management. A systematic review of the literature was undertaken using Medline, Embase, Pubmed, Cochrane and Web of Science. Several small series have described sporadic cases with perianal cancer in Crohn’s disease. The incidence rate of SCC related to perianal fistula was very low (<1%). Prognosis was poor. Colorectal disease, chronic perianal disease and HPV infection were possible risk factors. Fistula-related carcinoma in CD (Chron’s disease) can be very difficult to diagnose. Examination may be limited by pain, strictures and induration of the perianal tissues. HPV is an important risk factor with a particular carcinogenesis mechanism. MRI can help clinicians in diagnosis. Examination under anesthesia is highly recommended when findings, a change in symptoms, or simply long-standing disease in the perineum are present. Future studies are needed to understand the role of HPV vaccination in preventing fistula-related cancer.

scholarly journals Targeted 1H NMR metabolomics and immunological phenotyping of human fresh blood and serum samples discriminate between healthy individuals and inflammatory bowel disease patients treated with anti-TNF

2021 ◽  
Author(s):  
Sara Notararigo ◽  
Manuel Martín-Pastor ◽  
Juan E. Viñuela Roldán ◽  
Adriano Quiroga ◽  
J. Enrique Dominguez-Munoz ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Clinical Practice ◽  
Crohn's Disease ◽  
T Lymphocyte ◽  
Fresh Blood ◽  
Serum Samples ◽  
Nmr Metabolomics ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease is a multifactorial etiology, associated with environmental factors that can trigger both debut and relapses. A high level of tumor necrosis factor-α in the gut is the main consequence of immune system imbalance. The aim of treatment is to restore gut homeostasis. In this study, fresh blood and serum samples were used to identify biomarkers and to discriminate between Crohn’s disease and ulcerative colitis patients under remission treated with anti-TNF. Metabolomics based on Nuclear Magnetic Resonance spectroscopy (NMR) was used to detect unique biomarkers for each class of patients. Blood T lymphocyte repertories were characterized, as well as cytokine and transcription factor profiling, to complement the metabolomics data. Higher levels of homoserine-methionine and isobutyrate were identified as biomarkers of Crohn’s disease with ileocolic localization. For ulcerative colitis, lower levels of creatine-creatinine, proline, and tryptophan were found that reflect a deficit in the absorption of essential amino acids in the gut. T lymphocyte phenotyping and its functional profiling revealed that the overall inflammation was lower in Crohn’s disease patients than in those with ulcerative colitis. These results demonstrated that NMR metabolomics could be introduced as a high-throughput evaluation method in routine clinical practice to stratify both types of patients related to their pathology. Key messages NMR metabolomics is a non-invasive tool that could be implemented in the normal clinical practice for IBD to assess beneficial effect of the treatment. NMR metabolomics is a useful tool for precision medicine, in order to sew a specific treatment to a specific group of patients. Finding predictors of response to IFX would be desirable to select patients affected by IBD. Immunological status of inflammations correlates with NMR metabolomics biomarkers.

scholarly journals Revealing immune responses in the Mycobacterium avium subsp. paratuberculosis-infected THP-1 cells using single cell RNA-sequencing

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254194
Author(s):  
Hong-Tae Park ◽  
Woo Bin Park ◽  
Suji Kim ◽  
Jong-Sung Lim ◽  
Gyoungju Nah ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Single Cell ◽  
Mycobacterium Avium ◽  
Expression Patterns ◽  
Cell Types ◽  
Marker Genes ◽  
Specific Marker ◽  
Cell Type ◽  
Cytokines And Chemokines

Mycobacterium avium subsp. paratuberculosis (MAP) is a causative agent of Johne’s disease, which is a chronic and debilitating disease in ruminants. MAP is also considered to be a possible cause of Crohn’s disease in humans. However, few studies have focused on the interactions between MAP and human macrophages to elucidate the pathogenesis of Crohn’s disease. We sought to determine the initial responses of human THP-1 cells against MAP infection using single-cell RNA-seq analysis. Clustering analysis showed that THP-1 cells were divided into seven different clusters in response to phorbol-12-myristate-13-acetate (PMA) treatment. The characteristics of each cluster were investigated by identifying cluster-specific marker genes. From the results, we found that classically differentiated cells express CD14, CD36, and TLR2, and that this cell type showed the most active responses against MAP infection. The responses included the expression of proinflammatory cytokines and chemokines such as CCL4, CCL3, IL1B, IL8, and CCL20. In addition, the Mreg cell type, a novel cell type differentiated from THP-1 cells, was discovered. Thus, it is suggested that different cell types arise even when the same cell line is treated under the same conditions. Overall, analyzing gene expression patterns via scRNA-seq classification allows a more detailed observation of the response to infection by each cell type.

scholarly journals An Inter-Species Translation Model Implicates Integrin Signaling in Infliximab-Resistant Colonic Crohn’s Disease

2019 ◽  
Author(s):  
Douglas. K. Brubaker ◽  
Manu. P. Kumar ◽  
Paige. N. Vega ◽  
Austin. N. Southard-Smith ◽  
Alan. J. Simmons ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Animal Models ◽  
Crohn's Disease ◽  
Cell Types ◽  
Therapy Resistance ◽  
Integrin Signaling ◽  
Proteomics Data ◽  
Collagen Binding ◽  
Translation Model ◽  
Single Cell Rna Sequencing

AbstractAnti-TNF therapy resistance is a major clinical challenge in Crohn’s Disease (CD), partly due to insufficient understanding of disease-site, protein-level mechanisms of CD and anti-TNF treatment resistance. Although some proteomics data from CD mouse models exists, data type and phenotype discrepancies contribute to confounding attempts to translate between preclinical animal models of disease and human clinical cohorts. To meet this important challenge, we develop and demonstrate here an approach called Translatable Components Regression (TransComp-R) to overcome inter-species and trans-omic discrepancies between CD mouse models and human subjects. TransComp-R combines CD mouse model proteomic data with patient pre-treatment transcriptomic data to identify molecular features discernable in the mouse data predictive of patient response to anti-TNF therapy. Interrogating the TransComp-R models predominantly revealed upregulated integrin pathway signaling via collagen-binding integrin ITGA1 in anti-TNF resistant colonic CD (cCD) patients. Toward validation, we performed single-cell RNA sequencing on biopsies from a cCD patient and analyzed publicly available immune cell proteomics data to characterize the immune and intestinal cell types contributing to anti-TNF resistance. We found that ITGA1 is indeed expressed in colonic T-cell populations and that interactions between collagen-binding integrins on T-cells and colonic cell types expressing secreted collagens are associated with anti-TNF therapy resistance. Biologically, TransComp-R linked previously disparate observations about collagen and ITGA1 signaling to a potential therapeutic avenue for overcoming anti-TNF therapy resistance in cCD. Methodologically, TransComp-R provides a flexible, generalizable framework for addressing inter-species, inter-omic, and inter-phenotypic discrepancies between animal models and patients to deliver translationally relevant biological insights.One Sentence SummaryBrubaker et al. implicate dysregulated collagen-binding integrin signaling in resistance to anti-TNF therapy in Crohn’s Disease by developing a mouse-proteomic to human-transcriptomic translation model and confirm the associated inter-cellular signaling network using single-cell RNA sequencing.

scholarly journals P615 Efficacy of vedolizumab in patients with Crohn's disease may differ depending on the disease location: The UCLH experience

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S420-S421
Author(s):  
T Kumagai ◽  
M Vinayaga-Pavan ◽  
I Parisi ◽  
J Barragry ◽  
R Sundramoorthi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Location

scholarly journals Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn’s Disease: A Post Hoc Analysis From the CALM Study

2020 ◽  
Vol 26 (10) ◽  
pp. 1562-1571 ◽  
Author(s):  
Walter Reinisch ◽  
Remo Panaccione ◽  
Peter Bossuyt ◽  
Filip Baert ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Surrogate Marker ◽  
Fecal Calprotectin ◽  
Sensitivity Analyses ◽  
End Points ◽  
Predictive Values ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Disease Location

Abstract Background CALM was a randomized phase 3 trial in patients with Crohn’s disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) &lt;4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP &lt;5 mg/L or ≥5 mg/L and FC &lt;250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test. Results The proportion of patients who achieved the primary end point CDEIS &lt;4 and no deep ulcers was significantly greater for those with FC &lt;250 µg/g (74%; P &lt; 0.001), with an additive effect for CRP &lt;5 mg/L. The association of FC &lt;250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin &lt;250 µg/g, CRP &lt;5 mg/L, and CDAI &lt;150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS &lt;4 and no deep ulcers 48 weeks after randomization. Conclusion This post hoc analysis of CALM demonstrated that a cutoff of FC &lt;250 µg/g is a useful surrogate marker for mucosal healing in CD.

scholarly journals P128 Diagnostic accuracy of faecal calprotectin in Crohn's disease – Does disease location matter?

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S141-S142
Author(s):  
E. Simon ◽  
R. Wardle ◽  
A.A. Thi ◽  
J. Eldridge ◽  
S. Samuel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Diagnostic Accuracy ◽  
Faecal Calprotectin ◽  
Disease Location

Su1805 - Fecal Calprotectin is Highly Effective to Detect Endoscopic Ulcerations in Crohn's Disease Regardless of Disease Location

2018 ◽  
Vol 154 (6) ◽  
pp. S-590-S-591 ◽  
Author(s):  
Anthony Buisson ◽  
Wing Yan Mak ◽  
Michael J. Andersen ◽  
Donald Lei ◽  
Joel R. Pekow ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fecal Calprotectin ◽  
Highly Effective ◽  
Disease Location

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study

2020 ◽  
Vol 58 (05) ◽  
pp. 439-444 ◽  
Author(s):  
Anne Kerstin Thomann ◽  
Lucas-Alexander Schulte ◽  
Anna-Maria Globig ◽  
Peter Hoffmann ◽  
Thomas Klag ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Pilot Study ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Roc Curve ◽  
Response To Therapy ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Area Under Roc Curve

Abstract Background and aim The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn’s disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16. Methods Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration. Results Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001). Conclusion Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.

Sign in / Sign up

Export Citation Format

Share Document