Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody.

Przemioslo, Robert; Lundin, Knut E.A.; Sollid, Ludvig M.; Nelufer, J.M.; Ciclitira, Paul J.

doi:10.1136/gut.36.6.874

Cited by 106 publications

(59 citation statements)

References 24 publications

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“…We believe that effects of local, gliadin induced T cell activation can explain much of the small intestinal damage. For instance, the small intestinal epithelial changes seen in untreated CD are mimicked by cytokines produced by gliadinactivated TCC [29,30]. However, many observations remain unexplained and the rapid small intestinal changes seen after gliadin challenge are probably not induced by gliadin specific T cells [5,31,32].…”

Section: Discussionmentioning

confidence: 99%

Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls

Kett²,

et al. 1997

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The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.

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Section: Discussionmentioning

confidence: 99%

Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls

Kett²,

et al. 1997

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“…The recently described lack of association of MMP-1 and MMP-3 genes with CD 37 points to a crucial role of mucosal regulation of MMP. IFN-g appears to be the culprit of the observed MMP-12 upregulation and confirmation of its relevance in CD pathogenesis has been indirectly provided by the finding that anti-IFN-g antibodies can prevent villous atrophy both in CD mucosal samples treated with the supernatants of gliadin-activated T-cell clones 38 and in murine graft-vs-host-disease, 39 a condition that shares many features in common with CD.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase pattern in celiac duodenal mucosa

Ciccocioppo

Sabatino

Bauer

et al. 2005

Laboratory Investigation

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Matrix metalloproteinases (MMPs) are a family of endopeptidases playing a key role in tissue remodelling in both physiological and pathological conditions. Since little information is available about their role in celiac disease (CD), our aims were to quantify their expression/activity and to investigate their relation to proinflammatory cytokines in this condition. Duodenal biopsies from untreated, treated celiac patients and controls were used to quantify the expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, MMP-14, their inhibitor TIMP-1, IFN-c and TNF-a by using real-time reverse transcription-polymerase chain reaction and the gelatin/casein/elastin activities by gel zymography, and to isolate lamina propria mononuclear cells (LPMCs). These cells and myofibroblasts isolated from jejunal specimens were incubated in the absence or presence of IFN-c and TNF-a. MMP-1 and MMP-12 mRNA levels were significantly increased in active CD compared to treated (Po0.01 and Po0.0005, respectively) and normal mucosa (Po0.01 and Po0.0005, respectively), and this was paralleled by an upregulation of caseinolytic and elastolytic activities. Furthermore, MMP-12 levels significantly (Po0.05) correlated with those of IFN-c and the degree of villous flattening. MMP-2 turned out to be significantly (Po0.05) reduced in untreated and treated celiacs compared to controls. In active CD, transcripts of TIMP-1 were higher than in treated and controls (Po0.005 and Po0.05, respectively), such as those of IFN-c (Po0.05), whereas TNF-a levels were suppressed (P ¼ 0.0001). In physiological condition, myofibroblasts represent the main source of MMP-2, whereas LPMCs produce almost all MMPs only after cytokine stimulation. Conversely, cells isolated from active patients constitutively express MMPs without any increase after cytokine stimulation, while those from treated patients are in a resting condition. In conclusion, our results show the presence of a peculiar MMP pattern in active CD strongly dominated by MMP-12, correlating either with IFN-c or the degree of mucosal damage.

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“…Serum samples were obtained when the first biopsy was taken (untreated coeliac disease), in remission on a gluten-free diet (treated), and/or at relapse after reintroduction of gluten (challenged). Anti-blactoglobulin antibody levels and avidities were analysed in sera from 16 children with untreated disease (median age 12 months, range [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and nine with treated disease (median age 35 months, range . Antigliadin antibody levels and avidities were measured in 16 untreated coeliac children (median age 15 months, range 10-24), 11 treated cases (median age 32 months, range 17-57) and in eight coeliac children at relapse on gluten challenge (median age 45 months, range 32-53).…”

Section: Patientsmentioning

confidence: 99%

Avidity progression of dietary antibodies in healthy and coeliac children

Saalman

Dahlgren

Fällström

et al. 2003

Clinical and Experimental Immunology

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SUMMARYIn most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. b -lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and antigen, often increases during antibody responses and may be related to the biological effectiveness of antibodies. The aim of the present study was to determine the avidity of serum IgG antibodies against b -lactoglobulin and gliadin in healthy children during early childhood and compare these avidities to those found in children with coeliac disease. The average antibody avidity was analysed using a thiocyanate elution assay, whereas the antibody activity of the corresponding sera was assayed by ELISA. The avidity of serum IgG antibodies against b -lactoglobulin as well as gliadin increased with age in healthy children, even in the face of falling antibody titres to the same antigens. Children with untreated coeliac disease had IgG anti-b -lactoglobulin antibodies of significantly higher avidity than healthy children of the same age, and the same trend was observed for IgG antigliadin antibodies. The present data suggest that the avidities of antibodies against dietary antigens increase progressively during early childhood, and that this process seems to be accelerated during active coeliac disease.

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Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody.

Abstract: The isolation of gliadin specific HLA-DQ2

Cited by 106 publications

References 24 publications

Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls

Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls

Matrix metalloproteinase pattern in celiac duodenal mucosa

Avidity progression of dietary antibodies in healthy and coeliac children

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