Activation of the mucosal immune system in irritable bowel syndrome

Chadwick, V. S.; Chen, Wangxue; Shu, Dairu; Paulus, Barbara; Bethwaite, Peter; Tie, Andy; Wilson, Ian

doi:10.1053/gast.2002.33579

Cited by 697 publications

(571 citation statements)

References 17 publications

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“…Recently, the role of microscopic inflammation and immune activation in the intestinal mucosa has been elucidated. 3,5,22 Gastrointestinal infections are more likely to initiate IBS-like symptoms 23 inducing mucosal inflammation. Impaired intestinal permeability 24 and a role for mucosal inflammation in regulating the gut-brain axis 25 have also been reported.…”

Section: Discussionmentioning

confidence: 99%

“…3 In fact, several studies have shown an increased number of immunocytes both in the lamina propria and in the epithelium of mucosal biopsy specimens from IBS patients. 4 -10 Lamina propria and intraepithelial lymphocytes, 5,10 mast cells, 4,7,9 and macrophages 11 are among the immunocytes involved in mucosal inflammation in IBS, and a role for a previous infectious enteritis in determining this inflammation has been established. 11,12 However, it is also known that dietary factors might be important in the pathogenesis of IBS 3 and the same inflammatory cells, together with eosinophils, are the immunologic effectors of food hypersensitivity (FH).…”

Section: Rritable Bowel Syndrome (Ibs) Is a Common Gastrointestinalmentioning

confidence: 99%

See 1 more Smart Citation

Fecal Assays Detect Hypersensitivity to Cow's Milk Protein and Gluten in Adults With Irritable Bowel Syndrome

Carroccio

Brusca

Mansueto

et al. 2011

Clinical Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 99%

Section: Rritable Bowel Syndrome (Ibs) Is a Common Gastrointestinalmentioning

confidence: 99%

Fecal Assays Detect Hypersensitivity to Cow's Milk Protein and Gluten in Adults With Irritable Bowel Syndrome

Carroccio

Brusca

Mansueto

et al. 2011

Clinical Gastroenterology and Hepatology

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“…Th erefore, immune cell infi ltration assessed in mucosal biopsies may provide critical information on the mechanisms of symptom generation. Both intestinal ( 4 ) and colonic ( 5,6 ) biopsies have been investigated. Mast cells have received particular attention because its secretory products, such as histamine, prostaglandins, and proteinases, are capable of sensorimotor dysfunction.…”

mentioning

confidence: 99%

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Theoharides¹,

Asadi²,

Chen³

et al. 2012

American Journal of Gastroenterology

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Irritable bowel syndrome (IBS) is the most common condition seen by gastroenterologists. It presents with alternating symptoms of bowel dysfunction that often worsens with stress. The cause of these symptoms eludes investigators and many attempts have been made to discover an underlying pathology. This is a daunting task since symptoms come and go, and change characteristics. Furthermore, the pathology of IBS is unlikely to be identical in all patients. In addition, all symptoms and all features studied thus far have a strong overlap with healthy volunteers. Elsewhere in this issue, Braak et al. report a well-designed clinical investigation in patients with IBS and come to the conclusion that IBS is not characterized by mast cell or other immune cell proliferation, but by immune dysregulation in the colon. Is this the fi nal answer? Am J Gastroenterol 2012; 107:727 -729; doi: 10.1038/ajg.2012 Irritable bowel syndrome (IBS) is a common functional disorder in the West ( 1 ) and in Asia ( 2 ), which is characterized clinically as abdominal discomfort or pain with alternating constipation and diarrhea. Mechanistic pathways to symptom generation are unclear, although dysfunction of brain-gut communication, gut motility, visceral perception, neuroimmune responses, infl ammation, and mucosal integrity, as well as the psychosocial status might be involved ( 3 ). Th e mucosa contains endings of the enteric sensory nerves; these aff erent nerves can modify motility and pain perception. Th erefore, immune cell infi ltration assessed in mucosal biopsies may provide critical information on the mechanisms of symptom generation. Both intestinal ( 4 ) and colonic ( 5,6 ) biopsies have been investigated. Mast cells have received particular attention because its secretory products, such as histamine, prostaglandins, and proteinases, are capable of sensorimotor dysfunction. IBS appears to worsen with stress and the important information might be obtained from relationships between stress, corticotropin-releasing hormone (CRH) and symptoms ( 7 ). CRH signaling pathways have been shown to have an important role in stress-related alterations of gut function related to intestinal symptoms ( 7 ). Braak et al. ( 8 ) have attempted to clarify IBS pathophysiology using these strategies.Mast cells are well known to modulate gastrointestinal pathophysiology and are considered to be involved in IBS ( 9 ). Increased numbers of mast cells have been reported in the terminal ileum in patients with IBS, although there was lack of correlation with diarrhea-predominant IBS symptoms ( 4 ). Braak et al. ( 8 ) conclude that the number of mast cells, macrophages (CD68), T cells (CD3 and CD8), and λ FLC-positive mast cells is decreased in IBS patients compared with healthy volunteers. As a general statement, this needs clarifi cation. Th ey note the decrease in the descending colon, but no change was seen in the ascending colon and immune cell numbers in the small intestine were not measured. Furthermore, mast cells in the gut musculature ( ...

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“…This evidence, based on extensive study of the Trichinella-infected jejunum of small experimental animals (Collins 1996;Barbara et al 1997) is supported by several studies in IBS that demonstrate increased numbers of intra-mucosal inflammatory cells including __________________________________________________________________________________ 21 mast cells (Barbara et al 2004;Wang et al 2004) and T lymphocytes (Spiller et al 2000;Chadwick et al 2002), as well as increased levels of pro-inflammatory mediators (Gonsalkorale et al 2003;O'Mahony et al 2005). Inflammatory cells have also been…”

Section: The Gi Tract As a Target For Autoimmunitymentioning

confidence: 68%

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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Dysfunction of the gastrointestinal neuromuscular apparatus (including interstitial cells ofCajal) is presumed to underlie a heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). Humoral (antibody)-mediated autoimmunity directed against ligand-or voltage-gated ion channels or associated proteins involved in neuromuscular transmission is associated with several acquired neuromuscular diseases of the periphery and is now implicated in an increasing number of less well-characterised diseases. Anti-channel antibodies have been reported in small numbers of patients with GINMD, particularly in those with GI dysfunction secondary to an underlying disease such as neoplasia or infection. However, little is known of humoral autoimmunity in primary GINMDs.This thesis investigated the association between anti-channel antibodies and GINMD, and the human GI tract as a potential target of anti-channel antibodies. The presence of antivoltage-and ligand-gated antibodies was investigated in the serum of patients with primary achalasia, enteric dysmotility and intestinal pseudo-obstruction, and in those with GINMD secondary to Chagas' disease. The functional effect of sera from some of these patients on colonic smooth muscle contractility was also characterised. Finally, the distribution of six voltage-gated potassium channels (VGKCs), which serve essential roles in the peripheral and central nervous systems and are known targets of pathological autoantibodies, were investigated in all layers of the human GI tract.Our findings suggest that currently recognised anti-channel antibodies are not a common pathogenic factor in primary GINMDs. Anti-channel antibodies, in particular anti-VGKC antibodies, were however found in a significant number of individuals with Chagas' disease. Furthermore, circulating factors in patients with chagasic GI disease altered GI smooth muscle contractility in vitro which may have pathological relevance to GI

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Activation of the mucosal immune system in irritable bowel syndrome

Cited by 697 publications

References 17 publications

Fecal Assays Detect Hypersensitivity to Cow's Milk Protein and Gluten in Adults With Irritable Bowel Syndrome

Fecal Assays Detect Hypersensitivity to Cow's Milk Protein and Gluten in Adults With Irritable Bowel Syndrome

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

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