Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease

Nilsen, Ellen M.; Jahnsen, Frode L.; Lundin, Knut E.A.; Johansen, Finn–Eirik; Fausa, O; Sollid, Ludvig M.; Jahnsen, Jørgen; Scott, Helge; Brandtzæg, Per

doi:10.1016/s0016-5085(98)70134-9

Cited by 422 publications

(370 citation statements)

References 50 publications

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“…Our data also indicate that in the gastrointestinal mucosa up-regulation of IL-12R␤2 occurs only in IL-12-associated diseases and suggest that IL-12 may directly influence the level of IL-12R␤2 on T cells. First, we detected transcripts for IL-12 in CD, HP-associated gastritis, and Salmonella colitis, but not in celiac disease, confirming the recent observation that IL-12 is undetectable in celiac disease mucosa (39). Second, we showed that a neutralizing IL-12 Ab dramatically down-regulated IL-12R␤2 expression in CD LPMC.…”

Section: Discussionsupporting

confidence: 86%

“…However, we were able to detect no increase in IL-12R␤2 in duodenal samples from patients with celiac disease, a gluten-sensitive Th1-mediated enteropathy (39,40). Our data also indicate that in the gastrointestinal mucosa up-regulation of IL-12R␤2 occurs only in IL-12-associated diseases and suggest that IL-12 may directly influence the level of IL-12R␤2 on T cells.…”

Section: Discussionmentioning

confidence: 45%

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Up-Regulation of the IL-12 Receptor β2 Chain in Crohn’s Disease

Parrello

Monteleone

Cucchiara

et al. 2000

The Journal of Immunology

121

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Crohn’ s disease (CD) is a chronic intestinal inflammatory disorder characterized by aberrant mucosal Th1 cell activation and production of IL-12, the major Th1-driving factor. The T cell response to IL-12 is dependent on the expression of a specific receptor composed of two subunits, termed IL-12Rβ1 and IL-12Rβ2. The content of IL-12Rβ2, as measured at the mRNA level, is crucial in regulating Th1 differentiation. In this study we therefore investigated IL-12Rβ2 RNA transcripts in CD. IL-12Rβ2 expression was increased in active CD as well as Helicobacter pylori (HP)-associated gastritis and Salmonella colitis compared with that in inactive CD, ulcerative colitis, noninflammatory controls, and celiac disease. In contrast, IL-12Rβ1 transcripts were expressed at comparable levels in all samples. In CD, IL-12Rβ2 expression strictly correlated with tyrosine phosphorylation of STAT4, a key component of the IL-12-dependent Th1 polarization. This was associated with a pronounced expression of IFN-γ. Transcripts for IL-12/p40 were detected in CD, HP-positive, and Salmonella colitis patients, but not in celiac disease, indicating that IL-12Rβ2 up-regulation occurs only in IL-12-associated Th1 gastrointestinal diseases. Finally, we showed that stimulation of lamina propria mononuclear cells with IL-12 enhanced IL-12Rβ2, suggesting that IL-12 regulates IL-12Rβ2 expression in human gastrointestinal mucosa. The data show that the signaling pathway used by IL-12 to induce Th1 differentiation is increased at the site of disease in CD, further supporting the view that IL-12/IL-12R signals contribute to the inflammatory response in this condition.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 45%

Up-Regulation of the IL-12 Receptor β2 Chain in Crohn’s Disease

Parrello

Monteleone

Cucchiara

et al. 2000

The Journal of Immunology

121

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“…In healthy individuals, the inductive tissues of the gut normally maintain an immunosuppressive, Th2-predominant environment. This is not the case in patients with coeliac disease, the prototype wheat-induced immune disorder, which involves IFN-γ-related damage to the gut [38,39]. The present study shows that this is also the case in young BBdp rats.…”

Section: Discussioncontrasting

confidence: 46%

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Chakir¹,

Lefebvre

Wang³

et al. 2005

Diabetologia

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Aims/hypothesis: Type 1 diabetes is the result of an inflammatory T helper 1 (Th1) lymphocyte-mediated beta cell destructive process. The majority of diabetesprone BioBreeding (BBdp) rats fed wheat protein-based diets, such as NTP-2000, develop type 1 diabetes and display a mild coeliac-like enteropathy. Mesenteric lymph nodes (MLNs), which drain the gut, are the major inductive site where dietary antigens are recognised in the gut-associated lymphoid tissue (GALT). We hypothesised that this compartment could be a site of abnormal wheat proteininduced Th1 cell activation. Methods: MLN cells were isolated from BBdp and BB control (BBc) rats that were fed NTP-2000 or a hydrolysed casein (HC)-based diet at ages that pre-date classic insulitis. The inflammatory status, phenotype and proliferation of these cells in response to wheat protein were determined. Results: The expression ratio of T-bet : Gata3, master transcription factors for Th1 and Th2 cytokines, was increased in the MLN from NTP-2000-fed BBdp rats compared with that from BBc rats, mainly due to decreased Gata3 expression. CD3 + CD4 + IFN-γ + T cells were more prevalent in the MLN of wheatfed BBdp rats, but remained at control levels in BBdp rats fed a diabetes-retardant HC diet. BBdp MLN cells proliferated in response to wheat protein antigens in a specific, dose-dependent manner, and >93% of cells were CD3 + CD4 + T cells. This proliferation was associated with a low proportion of CD4 + CD25 + T cells and a high proportion of dendritic cells in the MLN of BBdp rats. Conclusions/ interpretation: Before insulitis is established, the MLNs of wheat-fed BBdp rats contain an unusually high proportion of Th1 cells that proliferate specifically in response to wheat protein antigens.

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“…It is the trigger factor of celiac disease (CD), as it triggers an immune response by the T lymphocytes with subsequent production of cytokines, anti-gliadin antibodies (AGAs) and anti-tissue transglutaminase antibodies (anti-tTG) (1)(2)(3)(4). This cascade of events requires some predisposing situations, namely (in order of importance): intake of gluten with the diet, increased permeability of the intestinal mucosa, a predisposing genetic makeup characterized by the presence of HLA molecules of class II DQ2 or DQ8 (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic efficacy of the ELISA test for the detection of deamidated anti‐gliadin peptide antibodies in the diagnosis and monitoring of celiac disease

Tonutti

Visentini

Picierno

et al. 2009

Clinical Laboratory Analysis

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Background and Aim: We evaluated the diagnostic performance of an ELISA test for anti-gliadin IgA and IgG antibodies, which uses synthetic deamidated gliadin peptides (anti-gliadin antibodies, AGAs) as coating; the results were compared with a test that uses extracted gliadin (AGAe). Methods: The study was conducted on the sera of 144 patients suffering from celiac disease (CD), including 20 patients with IgA deficiency and 9 who were following a gluten-free diet (GFD), and 129 controls. Results: In the 115 CD patients (without IgA deficiency), the sensitivity of AGAe IgA and IgG was 32.2 and 60.9%, whereas that of AGAs IgA and IgG was 59.1 and 72.2%. The specificity for AGAe IgA and IgG, and AGAs IgA and IgG was 93.8 and 89.9%, and 96.9% and 99.2%, respectively. Of the 20 patients with CD and IgA deficiency, 7 tested positive for AGAe IgG and 14 for AGAs IgG. The test using deamidated gliadin peptides performed better in terms of sensitivity and specificity than the AGA tests with extracted antigen. Conclusions: The very high specificity of the AGAs IgG test (99.2%) also suggests that patients who test positive with this assay require a thorough followup, even if the anti-tissue transglutaminase antibodies (anti-tTG) and anti-endomysial autoantibodies (EMA) assays are negative.

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Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease

Cited by 422 publications

References 50 publications

Up-Regulation of the IL-12 Receptor β2 Chain in Crohn’s Disease

Up-Regulation of the IL-12 Receptor β2 Chain in Crohn’s Disease

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Diagnostic efficacy of the ELISA test for the detection of deamidated anti‐gliadin peptide antibodies in the diagnosis and monitoring of celiac disease

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