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Type: Journal article
Title: Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia
Author: Liebregts, T.
Adam, B.
Bredack, C.
Gururatsakul, M.
Pilkington, K.
Brierley, S.
Blackshaw, L.
Gerken, G.
Talley, N.
Holtmann, G.
Citation: American Journal of Gastroenterology, 2011; 106(6):1089-1098
Publisher: Blackwell Publishing Ltd
Issue Date: 2011
ISSN: 0002-9270
Statement of
Tobias Liebregts, Birgit Adam, Christoph Bredack, Montri Gururatsakul, Katherine R. Pilkington, Stuart M. Brierley, L. Ashley Blackshaw, Guido Gerken, Nicholas J. Talley, and Gerald Holtmann
Abstract: OBJECTIVES: Immune activation may have an important pathogenic role in the irritable bowel syndrome (IBS). While little is known about immunologic function in functional dyspepsia (FD), we have observed an association between cytokine secretion by peripheral blood mononuclear cells (PBMCs) and symptoms in IBS. Upper gastrointestinal inflammatory diseases are characterized by enhanced small bowel homing α4-, β7-integrin, chemokine receptor 9 (CCR9) positive T lymphocytes. We hypothesized that increased cytokine release and elevated circulating small bowel homing T cells are linked to the severity of symptoms in patients with FD. Thus, we aimed to (i) compare cytokine release in FD and healthy controls (HCs), (ii) quantify “gut homing” T cells in FD compared with HC and patients with IBS, and (iii) correlate the findings to symptom severity and gastric emptying. METHODS: PBMC from 45 (Helicobacter pylori negative) patients with FD (Rome II) and 35 matched HC were isolated by density gradient centrifugation and cultured for 24 h. Cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10) was measured by enzyme-linked immunosorbent assay. CD4+ α4β7+CCR9+ T cells were quantified by flow cytometry in FD, HC and 23 patients with IBS. Gastric emptying was measured by scintigraphy. Symptom severity was assessed utilizing the standardized Gastrointestinal Symptom Score. RESULTS: FD patients had significantly higher TNF-α (107.2±42.8 vs. 58.7±7.4 pg/ml), IL-1β (204.8±71.5 vs. 80.2±17.4 pg/ml), and IL-10 (218±63.3 vs. 110.9±18.5 pg/ml) levels compared with HC, and enhanced gut homing lymphocytes compared with HC or IBS. Cytokine release and CD4+α4β7+CCR9+ lymphocytes were correlated with the symptom intensity of pain, cramps, nausea, and vomiting. Delayed gastric emptying was significantly associated (r=0.78, P=0.021) with CD4+α4β7+CCR9+ lymphocytes and IL-1β, TNF-α, and IL-10 secretion. CONCLUSIONS: Cellular immune activation with increased small bowel homing T cells may be key factors in the clinical manifestations of H. pylori-negative FD.
Keywords: Intestine, Small
Leukocytes, Mononuclear
Cells, Cultured
Irritable Bowel Syndrome
Tumor Necrosis Factor-alpha
Receptors, Lymphocyte Homing
Biopsy, Needle
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Severity of Illness Index
Sensitivity and Specificity
Case-Control Studies
Gastric Emptying
Time Factors
Reference Values
Middle Aged
Rights: © 2011 by the American College of Gastroenterology
DOI: 10.1038/ajg.2010.512
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