scholarly journals Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases

2012 ◽  
Vol 18 (12) ◽  
pp. 2334-2341 ◽  
Author(s):  
Alan R. Harris ◽  
Dorottya Nagy-Szakal ◽  
Natalia Pedersen ◽  
Antone Opekun ◽  
Jiri Bronsky ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Diseases ◽  
Peripheral Blood ◽  
Peripheral Blood Leukocyte ◽  
Genome Wide ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Blood Leukocyte

IRF5 Acts as a Potential Therapeutic Marker in Inflammatory Bowel Diseases

2020 ◽  
Author(s):  
Yonghong Yang ◽  
Cui Zhang ◽  
Dehuai Jing ◽  
Heng He ◽  
Xiaoyu Li ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Activity ◽  
Inflammatory Bowel Diseases ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Orphan Receptor ◽  
Peripheral Blood Mononuclear ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammatory disorders. As is well known, interferon regulatory factor (IRF) 5 is closely associated with the pathogenesis of various inflammatory diseases. But the exact role of IRF5 in IBD remains unclear. Methods In this study, we detected IRF5 expression in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa from IBD patients by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction. Peripheral blood CD4+ T cells were stimulated with inflammatory cytokines and transfected by lentivirus. Results In active IBD patients, the expression of IRF5 in PBMCs and inflamed colonic tissues was obviously increased and significantly associated with disease activity. Ectopic overexpression of IRF5 could promote the differentiation of IBD CD4+ T cells into Th1 and Th17 cells by regulating T-bet and RAR related orphan receptor C, whereas knockdown of IRF5 had the opposite effects. Tumor necrosis factor (TNF)-α upregulated expression of IRF5 in CD4+ T cells, but anti-TNF treatment with infliximab could markedly reduce IRF5 expression in CD4+ T cells and intestinal mucosa of CD patients. Conclusion Our study reveals a novel mechanism that IRF5 levels are correlated with disease activity in IBD and might function as a possible marker for the management of IBD via regulating Th1 and Th17 immune responses and cytokine production.

Genome-Wide Scanning in Inflammatory Bowel Diseases

1998 ◽  
Vol 16 (6) ◽  
pp. 364-369 ◽  
Author(s):  
J.P. Hugot ◽  
G. Thomas
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Genome Wide ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Novel Evidence That Very Small Embryonic Like Stem Cells (VSELs) Are Mobilized Into Peripheral Blood in Patients with Inflammatory Bowel Diseases – Correlation with Young Age and Severity of Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4595-4595
Author(s):  
Wojciech Marlicz ◽  
Edyta Paczkowska ◽  
Maciek Halasa ◽  
Boguslaw Machaliñski ◽  
Teresa Starzynska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Pluripotent Stem Cells ◽  
Peripheral Blood ◽  
Young Age ◽  
Cxcr4 Receptor ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Abstract 4595 Introduction We have hypothesized that circulating pluripotent stem cells could play a protective role in the pathogenesis of inflammatory bowel diseases (IBD) and participate in regeneration of damaged intestinal eipthelium. Recently, our group has identified in murine and human BM as well as other organs a population of very small embryonic like stem cells (VSELs) (Leukemia 2006, 20, 857-69). These are cells deposited in BM during development, differentiate into cells from all three germ layers and are capable of long term repopulation of hematopoiesis. They also play an important role in turnover of tissue-specific/committed stem cells in various organs. We have also shown that the number of VSELs circulating in peripheral blood (PB) increases during stress and tissue/organ injury e.g., in patients after stroke (Stroke 2009, 40, 1237-1244) and myocardial infarction (JACC 2009, 53, 1-9). It is currently unknown whether VSELs are mobilized into PB in patients with IBD. Materials and Methods We evaluated the mobilization of VSELs into PB in patients with active IBD. There were twenty patients (n=20) enrolled with de novo diagnosed or untreated flare-ups with mild to moderate ulcerative colitis (Truelove and Witt's criteria) and Crohn's disease (Crohns Disease Activity Index) as well as age-matched healthy subjects (n=10). Blood was sampled on admission, erythrocytes were lysed and CXCR4+ CD133+ lin- CD45- VSELs were evaluated in PB by fluorescence-activated cell sorting analysis (FACS), direct immunofluorescence staining and real-time quantitative polymerase chain reaction to detect expression of developmentally early genes. Results In IBD patients, we found an increase in the number of circulating cells expressing stem cells-associated antigens such as CD133, CD34, and CXCR4. More important, we found an increase in the number of circulating primitive cells expressing the VSEL phenotype (CXCR4+ CD133+ in- CD45- cells - smaller than erythrocytes) (median 3.7 [range 0.9 to 8.9] cells/ml; p < 0.001) in comparison to healthy individuals (median 1.33 [range 0.2 – 1.45] cells/ml; p < 0.001 [Mann–Whitney test Friedman's ANOVA followed by Wilcoxon signed-rank test]). The mobilization of VSELs was higher in patients with active Crohn's disease and younger patients. Of note antimicrobial treatment also influenced the mobilization process. Circulating VSELs express pluripotent stem cell markers (Oct-4, SSEA-4, Nanog), CXCR4 receptor and respond robust to stromal derived factor-1 (SDF-1) gradient. We also noticed that the number of mobilized/circulating VSELs correlated in IBD patients with elevated serum level of CXCR4 receptor ligand - stromal derived factor -1 (SDF-1). Conclusions Using multiparameter analysis, we have demonstrated for the first time that VSELs could be detected in circulating PB of patients with active IBD. The number of this cell positively correlated with intensity of disease and young age. This strongly supports a potential involvement of circulating pluripotent stem cells in regeneration of damaged intestinal epithelium. However, the biological significance as well as potential application of these cells in regeneration of damaged gut tissue needs further investigations and is currently tested in animal models in our laboratories. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunological Variables Associated With Clinical and Endoscopic Response to Vedolizumab in Patients With Inflammatory Bowel Diseases

2020 ◽  
Vol 14 (9) ◽  
pp. 1190-1201 ◽  
Author(s):  
Marina Coletta ◽  
Moira Paroni ◽  
Maria Francesca Alvisi ◽  
Matilde De Luca ◽  
Eliana Rulli ◽  
...  
Keyword(s):  
Clinical Response ◽  
Lamina Propria ◽  
Inflammatory Bowel Diseases ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Multivariable Analysis ◽  
Response To Treatment ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Baseline Levels

Abstract Background and Aims Vedolizumab [VDZ] is a monoclonal antibody directed against the α4β7 integrin heterodimer, approved for patients with inflammatory bowel diseases [IBD]. This study aimed at identifying immunological variables associated with response to vedolizumab in patients with ulcerative colitis [UC] and Crohn’s disease [CD]. Methods This is a phase IV explorative prospective interventional trial. IBD patients received open-label VDZ at Weeks 0, 2, 6, and 14. Patients with a clinical response at Week 14 were maintained with VDZ up to Week 54. At Weeks 0 and 14, their peripheral blood was obtained and endoscopy with biopsies was performed. The Week 14 clinical response and remission, Week 54 clinical remission, and Week 14 endoscopic response were evaluated as endpoints of the study. The expression of surface markers, chemokine receptors, and α4β7 heterodimer in peripheral blood and lamina propria lymphocytes was assessed by flow cytometry. A panel of soluble mediators was assessed in sera at baseline and at Week 14 by 45-plex. Results A total of 38 IBD patients [20 UC, 18 CD] were included in the study. At Week 14, the clinical response and remission rates were 87% and 66%, respectively. Higher baseline levels of circulating memory Th1 cells were strongly associated with clinical response at Week 14 [p = 0.0001], whereas reduced baseline levels of lamina propria memory Th17 and Th1/17 cells were associated with endoscopic response. Immunological clusters were found to be independently associated with vedolizumab outcomes at multivariable analysis. A panel of soluble markers, including IL17A, TNF, CXCL1, CCL19 for CD and G-CSF and IL7 for UC, associated with vedolizumab-induced Week 54 clinical remission. Conclusions The results of this exploratory study uncovered a panel of circulating and mucosal immunological variables associated with response to treatment with vedolizumab.

Sign in / Sign up

Export Citation Format

Share Document