Taming the mucosal immune response in Crohn's disease

2002 ◽  
Vol 16 (6) ◽  
pp. 1035-1043 ◽  
Author(s):  
S.J.H. van Deventer
Keyword(s):  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Immune Response

scholarly journals P014 Identification of Crohn’s disease immunopathotypes

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
H M Baer ◽  
E MacDonald ◽  
A Ferguson ◽  
A M Scott ◽  
M I Khan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Local Immune Response ◽  
Cross Sectional ◽  
Treatment Responses ◽  
Colonic Biopsies

Abstract Background Crohn’s disease (CD) is a chronic inflammatory gastrointestinal condition, with globally increasing incidence. Patients with CD suffer from a loss of tolerance towards their commensal microbiota causing an aberrant immune response, occurring in a protracted relapse and remission cycle. Although a variety of frontline therapies is currently available, including targeted therapies such as biologic drugs, 30–40% of CD patients still require surgery to manage the disease. At present, the immunobiology of CD is not fully understood. However, differences in immune responses between patients might play an important role in diverse treatment responses. The aim of this study was to identify differences in peripheral and local immune responses of CD to understand differences in disease behaviour and treatment outcome. Methods Peripheral blood mononuclear cells and plasma were isolated from whole blood of a cross-sectional CD patient cohort (nCD = 12) and normal controls (NC, nNC = 28). Flow cytometry analysis and multiplex assays were used to quantify immune cell populations and cytokine levels, respectively. The local immune response was analysed by bulk RNA sequencing of mucosal colonic biopsies either from inflamed CD or normal tissue. Gene signatures were then followed up by validation in publicly deposited gene expression datasets (nCD = 36, nNC = 24), and by measurement of specific proteins using our archived samples. Results Peripheral immunophenotyping of the initial cross-sectional study displayed three different types of CD patients, characterised by either a decrease in leukocyte populations, an increase of cytokines, or a change in both. Analysis of the RNAseq data derived from colonic biopsies revealed four distinct clusters in genes associated with the immune response in CD patients. Further pathway analysis showed one cluster with an enriched B cell signature and another cluster with an elevated macrophage and neutrophil response. We utilised publicly available gene expression datasets to validate these signatures in a larger cohort and identified a selection of patients with an up-regulated pro-inflammatory macrophage response. Using correlation analysis, we suggest an immunopathotype with increased macrophage activation which is potentially associated with a more severe form of the disease. Conclusion We have identified distinct immunopathotypes in both the peripheral and local immune response of CD patients. Further investigation will correlate these distinct immune responses in CD with clinical parameters, to understand associations between diverse treatment responses and disease behaviours.

Tu1727 Inflammatory and Innate Immune Response Activated by Adherent-Invasive Escherichia coli Strains Isolated From Crohn's Disease Patients

2013 ◽  
Vol 144 (5) ◽  
pp. S-832 ◽  
Author(s):  
Rodrigo Quera ◽  
Marjorie De La Fuente ◽  
David Díaz-Jiménez ◽  
Roberto Vidal ◽  
Francisco López-Kostner ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Innate Immune Response ◽  
Innate Immune

scholarly journals Crohn’s Disease Patients in Remission Display an Enhanced Intestinal IgM+ B Cell Count in Concert with a Strong Activation of the Intestinal Complement System

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 78 ◽  
Author(s):  
Sophie Preisker ◽  
Ann-Kathrin Brethack ◽  
Arne Bokemeyer ◽  
Dominik Bettenworth ◽  
Christian Sina ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Complement System ◽  
Expression Patterns ◽  
Critical Role ◽  
Mucosal Immune Response ◽  
Immunoglobulin M ◽  
Complement Components ◽  
Activation Pathways ◽  
Definition Of

Inflammatory bowel disease (IBD) is an umbrella term that comprises Crohn’s disease (CD) and ulcerative colitis (UC). Both entities are characterized by a disturbed mucosal immune response and an imbalance of intestinal microbiota composition. The complement system (C) plays a critical role in the detection, and clearance of bacteria and dysregulation of single complement components has been linked to IBD. Here, we asked if the C contributes to distinct subtypes of inflammation observed in CD and UC. We performed systematical expression analyses of the intestinal C in IBD patients and controls. Immunohistochemistry or immunoblot experiments were performed to verify qPCR data. Activity of the three activation pathways of C was studied in sera samples. In CD patients a strong upregulation of the C was observed enabling the definition of unique expression patterns being associated either with remission or active disease. These data were reflected by an enhanced C activation in sera and fecal samples. An excessive mucosal presence of immunoglobulin M (IgM) and CR2/CD21 positive B cells in concert with decreased fecal IgA level was identified in CD patients in remission. These findings point to an exacerbated induction of the intestinal C that may potentially be involved in the etiology of CD.

T1222 NOD2-Mediated Innate Immune Response in Mucosal Biopsies of Children with Active Crohn's Disease

2008 ◽  
Vol 134 (4) ◽  
pp. A-510
Author(s):  
Laura Stronati ◽  
Anna Negroni ◽  
Maria Pierdomenico ◽  
Ilaria Menghi ◽  
Giulia Maiella ◽  
...  
Keyword(s):  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Innate Immune Response ◽  
Innate Immune

scholarly journals Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn’s disease

2002 ◽  
Vol 61 (1) ◽  
pp. 123-130 ◽  
Author(s):  
Miranda C. E. Lomer ◽  
Richard P. H. Thompson ◽  
Jonathan J. Powell
Keyword(s):  
Crohn’S Disease ◽  
Gastrointestinal Tract ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Ultrafine Particles ◽  
Activity Index ◽  
Food Additives ◽  
Disease Activity Index ◽  
Mucosal Immune Response ◽  
Double Blind

Crohn’s disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0·1–1·0 µm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn’s disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 1012 particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn’s disease, with a significant (P = 0·002) improvement in the Crohn’s disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.

scholarly journals Treatment of Refractory Crohn's Disease and Pyoderma Gangrenosum with a Combination Regimen of Rifaximin, Gentamicin and Metronidazole

2015 ◽  
Vol 9 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Neil D. Goldberg ◽  
Aravinda Vadlamudi ◽  
Nicole Parrish
Keyword(s):  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Pyoderma Gangrenosum ◽  
Standard Therapy ◽  
Combination Regimen ◽  
Gut Flora ◽  
Abnormal Immune Response ◽  
Infectious Etiology

The etiology of Crohn's disease (CD) remains controversial. It is hypothesized that CD is the result of an abnormal immune response to the gut flora in genetically susceptible hosts. However, an infectious etiology has not been completely ruled out. Antibiotics have been utilized with some success to modify the course of the disease. Here, we report a patient with CD and pyoderma gangrenosum refractory to standard therapy, including biologics, who achieved remission with a combination of rifaximin, gentamicin and metronidazole.

scholarly journals Proteomic Analysis of the Inflamed Intestinal Mucosa Reveals Distinctive Immune Response Profiles in Crohn’s Disease and Ulcerative Colitis

2007 ◽  
Vol 179 (1) ◽  
pp. 295-304 ◽  
Author(s):  
Uta Berndt ◽  
Sebastian Bartsch ◽  
Lars Philipsen ◽  
Silvio Danese ◽  
Bertram Wiedenmann ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Mucosa ◽  
Proteomic Analysis ◽  
Response Profiles

scholarly journals Amyloidosis and Renal Disease in Patients with Crohn's Disease

2020 ◽  
Author(s):  
Roberto Navarro Quiroz ◽  
Gustavo Aroca Martinez ◽  
Linda Atencio Ibarra ◽  
Maria Ospino Rodriguez ◽  
Joany Sarmiento Gutierrez ◽  
...  
Keyword(s):  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Renal Disease ◽  
Immune Cell ◽  
Humoral Immune ◽  
Commensal Microbiota ◽  
Pathological Alteration ◽  
Mesh Terms ◽  
Immune Defects

Crohn's disease (CD) results from an aberrant immune response against commensal microbiota in genetically susceptible hosts. However, the nature of immune defects, the microflora involved, and genetic susceptibility remain incompletely defined and controversial. This review seeks to describe the present state of association between CD and renal disease; moreover, we highlight the convergence of CD with amyloidosis that can trigger sustained inflammation, producing the pathological alteration observed in both diseases. The following MESH terms were searched in PubMed, PubMed Central (PMC), and Web of Science: “Crohn´s disease” and “renal disease.” The R RISmed package was used for PubMed and PMC. The abnormal humoral immune response is described along with alterations in immune cell migration mechanisms in CD during inflammation.

Sign in / Sign up

Export Citation Format

Share Document