Profiling of Human Circulating Dendritic Cells and Monocyte Subsets Discriminates Between Type and Mucosal Status in Patients With Inflammatory Bowel Disease

2020 ◽  
Author(s):  
Lorena Ortega Moreno ◽  
Samuel Fernández-Tomé ◽  
María Chaparro ◽  
Alicia C Marin ◽  
Irene Mora-Gutiérrez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Bowel Disease ◽  
Study Groups ◽  
Disease Diagnosis ◽  
Monocyte Subsets ◽  
Healthy Control ◽  
Inflammatory Bowel ◽  
Classical Monocytes

Abstract Background Intestinal dendritic cells (DC) and macrophages drive disease progression in patients with inflammatory bowel disease (IBD). We aimed to characterize the activation and homing profile of human circulating DC and monocyte subsets in healthy control patients (CP) and IBD patients. Methods Eighteen CP and 64 patients with IBD were categorized by diagnoses of Crohn disease (CD) and ulcerative colitis (UC), either endoscopically active (inflamed) or quiescent. Circulating type 1 conventional DC, type 2 conventional DC, plasmacytoid DC, classical monocytes, nonclassical monocytes, and intermediate monocytes were identified by flow cytometry in each individual and characterized for the expression of 18 markers. Association between DC/monocytes and IBD risk was tested by logistic regression. Discriminant canonical analyses were performed to classify the patients in their own endoscopy category considering all markers on each subset. Results CCRL1, CCR3, and CCR5 expression on circulating type 1 DC; CCRL1 expression on nonclassical monocytes; and CCR9 and β7 expression on classical monocytes allowed us to discriminate among the different study groups. Indeed, the same markers (excluding β7) were also associated with IBD when all DC and monocyte subsets were considered at the same time. Conclusions Monitoring the phenotype of human circulating DC and monocyte subsets may provide novel tools as biomarkers for disease diagnosis (CD/UC) or mucosal status (inflamed/noninflamed) in the absence of an invasive colonoscopy.

scholarly journals P045 Profiling of human circulating dendritic cells and monocytes subsets discriminates type and mucosal status in patients with inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S155-S156
Author(s):  
L Ortega Moreno ◽  
S Fernández Tomé ◽  
M Chaparro ◽  
A Marin ◽  
I Mora Gutiérrez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Bowel Disease ◽  
Strong Association ◽  
Inverse Association ◽  
Monocyte Subsets ◽  
Activation Markers ◽  
Potential Implication ◽  
Inflammatory Bowel ◽  
Classical Monocytes

Abstract Background Intestinal dendritic cells (DCs) and macrophages govern the mechanisms of immune homeostasis having a role in inflammatory bowel disease (IBD) onset. However, the profile of their circulating precursors (DC and monocytes) in IBD has not been previously described in depth. Our aim was to characterise blood DC and monocyte subsets in healthy controls (HCs) and IBD patients in order to understand their potential implication in IBD pathogenesis. Methods 18 HC and 64 IBD patients were recruited. IBD patients were categorised into Crohn’s disease (CD) and ulcerative colitis (UC), either endoscopically active (aCD and aUC) or quiescent (qCD and qUC), based on the SES-CD or the Mayo index endoscopic subscore. Blood circulating type 1 conventional DC (cDC1), type 2 conventional DC (cDC2), plasmacytoid DC (pDC), classical monocytes, non-classical monocytes and intermediate monocytes were identified by flow cytometry and characterised for the expression of 18 homing and activation markers (β7, CCR1, CCR2, CCR3, CCR5, CCR6, CCR7, CCR9, CCRL1, CD40, CD86, CD137L, CD274 (PD-L1), CLA, CXCR1, CXCR3, ICOSL and HLA-DR). Association between markers and the presence, type or activity of IBD was tested by logistic regression. Discriminant canonical analysis was also performed to classify the patients on their own endoscopy category. Results All groups (HC, aCD, qCD, aUC and qUC) were separated from the others based on the discriminant canonical analyses of the 18 markers applied over all DC and monocytes subsets (Figure 1). Specifically, CCRL1, CCR3 and CCR5 expression on cDC1, CCRL1 on non-classical monocytes and CCR9 and b7 on classical monocytes were highly associated to IBD. CCR3 displayed an odds ratio (OR) of 2.29 along with its 95% confidential interval (CI) between 1.11 and 4.75, showing a strong association with activity in CD; whereas the other markers displayed an inverse association with IBD. Hence, expression of CCRL1 on cDC1 and non-classical monocytes from aUC showed an OR (95% CI) of 0.23 (0.08–0.66) and 0.52 (0.28–0.95), respectively. In the case of qUC, CCR5 on cDC1 and β7 on classical monocytes displayed an OR (95% CI) of 0.10 (0.01–0.83) and 0.56 (0.34–0.90), respectively. CCR9 was inversely associated to qCD with an OR (95% CI) of 0.64 (0.46–0.89) in the classical monocytes subset. Indeed, the same markers (excluding β7) were also associated with IBD when all DC and monocyte subsets were considered at the same time. Conclusion Differences on the expression of migration markers CCR3, CCR5, CCR9, b7 and decoy receptor CCRL1 on circulating DC and monocyte subsets from IBD groups suggest the presence of constitutive migratory differences underlying IBD pathogenesis in CD or UC and its condition (inflamed or non-inflamed).

scholarly journals Prevalence of Joint Hypermobility and Patterns of Articular Manifestations in Patients with Inflammatory Bowel Disease

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
P. Vounotrypidis ◽  
E. Efremidou ◽  
P. Zezos ◽  
M. Pitiakoudis ◽  
E. Maltezos ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Study Groups ◽  
Joint Hypermobility ◽  
Fisher Exact Test ◽  
Hypermobility Syndrome ◽  
Exact Test ◽  
Significant Difference ◽  
Healthy Control ◽  
Inflammatory Bowel

Objective. The objective is the investigation of Joint Hypermobility (JH) and the Hypermobility Syndrome (HMS) in patients with inflammatory bowel disease (IBD).Methods. We examined 83 patients with IBD and 67 healthy individuals for the presence of JH. Patients were excluded if they were under 18 or over 50 years of age and if they had other conditions which affect joint mobility. Thex2and the Fisher exact test were used appropriately between study groups. Odds ratios (ORs) for the risk of JH and HMS in IBD groups were calculated.Results. A total of 150 individuals (83 IBD patients and 67 healthy controls) participated in the study. 69 IBD patients, 41 with Crohn's Disease (CD) and 28 with ulcerative colitis (UC), were finally eligible. JH was detected in 29 CD patients (70.7%), in 10 UC patients (35.7%), and in 17 healthy control subjects (25.4%). Significant difference was detected on JH in CD patients as compared to UC patients (P=.0063) and controls (P<.0001). The estimated OR for JH was 7.108 (95% CI: 2.98–16.95) in CD and 1.634 (95% CI: 0.63–4.22) in UC patients. HMS was detected in 5 (12.2%) CD and in 1 (3.57%) UC patients. The OR for HMS in CD was 3.75 (95% CI: 0.41–34.007), while 7 (17.1%) CD patients had overlapping symptoms for both HMS and early spondylarthropathy.Conclusions. JH and the HMS are common in CD patients, thus articular manifestations should be carefully interpreted. This implies an involvement of collagen varieties in the pathogenesis of IBD.

scholarly journals Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1083
Author(s):  
Aleksandra Filimoniuk ◽  
Agnieszka Blachnio-Zabielska ◽  
Monika Imierska ◽  
Dariusz Marek Lebensztejn ◽  
Urszula Daniluk
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Study Groups ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Specificity And Sensitivity ◽  
Potential Biomarker ◽  
Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

Decreased bone density in inflammatory bowel disease is related to corticosteroid use and not disease diagnosis

2009 ◽  
Vol 10 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Charles N. Bernstein ◽  
Leanne L. Seeger ◽  
James W. Sayre ◽  
Peter A. Anton ◽  
Lucy Artinian ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bone Density ◽  
Bowel Disease ◽  
Disease Diagnosis ◽  
Inflammatory Bowel

Inflammatory Bowel Disease: Diagnosis and Evaluation

2009 ◽  
pp. 739-756
Author(s):  
David E. Beck ◽  
Patricia L. Roberts ◽  
John L. Rombeau ◽  
Michael J. Stamos ◽  
Steven D. Wexner
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Disease Diagnosis ◽  
Inflammatory Bowel

scholarly journals P019 Colonic mucosal kinase activity, cytokine and chemokine profiles in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S139-S140
Author(s):  
E Brand ◽  
B Roosenboom ◽  
B Malvar Fernandez ◽  
L Lutter ◽  
E van Koolwijk ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kinase Activity ◽  
Cell Signalling ◽  
Explant Culture ◽  
Janus Kinase ◽  
Oncostatin M ◽  
Healthy Control ◽  
Inflammatory Bowel ◽  
The Difference

Abstract Background With the approval of tofacitinib, an oral Janus Kinase (JAK) inhibitor, modulation of kinase activity has been added to the therapeutic armamentarium of inflammatory bowel disease (IBD). Despite its established efficacy, at least a third of patients will not respond to this or other therapeutic options such as anti-tumour necrosis factor (TNF), anti-interleukin (IL)23/IL12 compounds or vedolizumab. A better understanding of the inflammatory profile could aid in tailoring drugs to individual patients. We therefore explored mucosal cytokine, chemokine and kinase activity profiles in IBD. Methods Colonic mucosal biopsies were collected from (1) patients with Crohn’s disease (CD, N = 8), (2) patients with ulcerative colitis (UC, N = 8) and (3) healthy controls (N = 4). IBD samples were collected both from inflamed and non-inflamed tissue from the same patients. All IBD patients were biological-naïve and had not used corticosteroids in the past 3 months. Biopsies were snap frozen for later kinase activity determination or directly used in a 24-h explant culture. Whole biopsy kinase activity (tyrosine, serine and threonine kinases) was assessed using the Pamgene platform. A 64-analyte panel was examined in the supernatant of the cultured biopsies employing a multiplex assay (Luminex). Results Whole-biopsy kinase activity differed between inflamed and non-inflamed mucosa of IBD patients, with more overall tyrosine kinase activity in inflamed mucosa in UC, and serine/threonine kinase activity in inflamed mucosa in CD as compared with non-inflamed mucosa (Figure 1). The kinase activity profile of non-inflamed mucosa of CD and UC patients was similarly different from mucosa of healthy control participants (Figure 2). The cytokine and chemokine profile of inflamed biopsies differed from non-inflamed IBD biopsies and healthy control biopsies, with higher levels of S100A8, TNFα, IL-6, oncostatin M (OSM) and triggering receptor expressed on myeloid cells-1 (TREM-1), amongst others (Figure 3). Conclusion In IBD, inflammation in the mucosa can be characterised both by explant-culture and kinase activity assessment. The difference in kinase activity between non-inflamed IBD mucosa and healthy control mucosa suggests the presence of sub-clinical alterations in cell signalling. The observed differences in the kinase, cytokine and chemokine profiles underscore the importance of this approach in the elucidation of the pathophysiology in IBD.

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