Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007570 (celiac disease)
 13,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coeliac disease is apparently a T cell-mediated disease, precipitated in the proximal small intestine of susceptible individuals by gluten. Preferential presentation of gluten peptides most probably takes place in coeliac mucosa by the disease-associated HLA-DQ2 and -DQ8 molecules. In peripheral blood, however, both HLA-DR, -DQ and -DP-restricted T cell responses to gluten have been observed. We examined gluten-specific T cell clones (TCC) derived from peripheral blood for cytokine production to see if their profiles were related to the HLA restriction or the disease state of the donors. As previously found for mucosal TCC, the main product was interferon-gamma (IFN-gamma), often with additional IL-4, IL-5, IL-6, IL-10, tumour necrosis factor, and transforming growth factor-beta. Regardless of restriction element or disease state, gluten-reactive TCC from peripheral blood therefore seem to secrete cytokines compatible with a Th0 profile.
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PMID:Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls. 856 15

The aim of this work was to investigate the mechanism of spontaneous rat liver allograft tolerance. Liver allografts from a LEW donor into DA recipient (LEW-->DA) or of PVG-->DA were spontaneously tolerated (TOL) across a complete MHC mismatch. In contrast, DA-->LEW or PVG-->LEW liver allografts were rejected in 10 to 15 days (REJ). We examined whether donor cell migration to recipient lymphoid tissues might be associated with TOL. Many donor cells were observed in draining (celiac) lymph nodes (LN) and spleen, reaching a peak on day 1 and then decreasing rapidly thereafter. Irradiation of liver donors, which we have previously shown to delete tolerance, significantly reduced the number of donor leukocytes in recipient lymphoid tissues. While this suggested an association between donor cell migration and tolerance, the number, distribution, and type of donor cells in recipient lymphoid tissues of REJ was similar to those of TOL. Expression of cytokine mRNA in LN and spleen showed an early increase in the expression of IL-2 and IFN-gamma mRNA on day 1 and then a rapid decrease to constitutive levels. Spleen and LN levels of IL-6, IL-10, TNF-alpha, or TGF-beta mRNA showed much less up-regulation than IL-2 or IFN-gamma. Paradoxically, there was greater expression of IL-2 and IFN-gamma mRNA in TOL lymphoid tissues than in REJ, and this superinduction was partially prevented by donor irradiation. Superinduction of IL-2 and IFN-gamma was, therefore, more closely associated with TOL than was donor cell migration. This was confirmed by treatment of TOL recipients with a short course of methylprednisolone, which reduced survival of subsequent donor strain skin grafts. This finding has implications for treatment of human liver transplants and is evidence for a novel pathway of transplant tolerance.
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PMID:Tolerance to rat liver allografts. III. Donor cell migration and tolerance-associated cytokine production in peripheral lymphoid tissues. 864 43

Eosinophils are not only the source of cytotoxic and proinflammatory mediators but they can also generate cytokines and growth factors, including their own factors of differentiation, namely IL-3, GM-CSF, and IL-5. Synthesis of IL-5 by eosinophils was demonstrated by in situ hybridization and immunostaining in a variety of diseases, such as coeliac disease, asthma, hypereosinophilic syndrome, or skin diseases. However, IL-5 synthesis by eosinophils was not shown in Crohn's disease, whereas in other diseases, it was restricted to a subpopulation of eosinophils, suggesting some heterogeneity in cytokine-producing eosinophils. Here, we report that human eosinophils, in addition to the synthesis of IL-5, and Th2 cytokine, can synthesize IFN gamma, a Th1 cytokine, as well as IL-10 and IL-4, known to be mainly produced by Th2 cells. Double immunostaining procedures reveal the coexpression of IL-5, IL-4, and IL-10 by the same eosinophil populations, different from IFN gamma-producing eosinophils. We propose that distinct subpopulations of human eosinophils express Th2 or Th1 cytokines. These results point to the importance of cytokines derived from non T cells in the regulation of the immune response.
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PMID:Synthesis of type 1 (IFN gamma) and type 2 (IL-4, IL-5, and IL-10) cytokines by human eosinophils. 890 27

Coeliac disease (CD), an inflammatory enteropathy, is believed to be caused by immune sensitivity to ingested gluten. T-cell activation appears to be implicated in the disease although little is known regarding the role of T-cell subsets, Th1/Th2, and the cytokines they secrete. Reverse transcription-polymerase chain reaction was used to examine the mRNA expression of a wide profile of cytokines in intestinal and peripheral samples taken from active and inactive CD paediatric patients. Differential mRNA expression was observed for cytokines, between CD patients and controls, in both compartments. The percentage of samples expressing interleukin (IL)-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, IL-10, IL-1beta, TNF-alpha and transforming growth factor (TGF)-beta mRNA from active CD patients was higher than from controls. A prominent finding was the expression of both Th1 (IFN-gamma, IL-2) and Th2 (IL-4, IL-10)-associated cytokine transcripts in the same biopsies and peripheral blood cells from patients with active CD implying activation of Th0 cells. The expression of IL-2 and IL-4 mRNA was not observed in peripheral blood samples from inactive CD patients associating them with disease activity. These results are important to the understanding of the inflammatory process in CD while cytokine levels may prove to be relevant markers of disease activity.
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PMID:Cytokine profile in coeliac disease. 1021 72

Coeliac disease (CoD) is a small intestinal disorder characterized by crypt cell hyperplasia and villous atrophy, and the production of cytokines from T cells and macrophages are of importance for the histological changes seen in CoD. A peroral immunization with an antigen, which gives rise to a mucosal immune response, may increase the levels of circulating cytokine-producing cells, and we wanted to obtain a better picture of an eventual emergence of activated circulating T cells in the peripheral blood in children with CoD. The cytokine expression of interferon-gamma (IFN-gamma), IL-4, IL-6 and IL-10 was measured at the single-cell level by an ELISPOT method in 38 children with CoD. The numbers of IFN-gamma-producing cells in the peripheral blood was increased in children with untreated CoD (P < 0.01) and after gluten challenge (P < 0.05) compared with healthy controls. Also, the numbers of IL-6-producing cells were increased (P < 0.05) after gluten challenge compared with the healthy controls. A paired comparison showed that the numbers of IFN-gamma-producing cells increased after gluten challenge (P < 0.05), whereas no such change was seen for IL-4- or IL-10-producing cells. There were no differences in the numbers of IFN-gamma-producing cells between the group of children with treated CoD and the groups of untreated or challenged CoD children. IL-4 production correlated with serum levels of total IgE. These results show that circulating mononuclear cells in children with active CoD secrete cytokines compatible with a type 1 response.
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PMID:Cytokine-producing cells in peripheral blood of children with coeliac disease secrete cytokines with a type 1 profile. 1033 14

The immune response of PBMC to gliadin was investigated in patients with coeliac disease (CoD) by examining proliferation, MHC restriction and cytokine production. Gliadin induced low levels of proliferation in 63% of eight untreated patients, 32% of 28 treated patients and 35% of 31 healthy control subjects. In MHC restriction studies, the proliferative response to gliadin was inhibited (range 47-98% inhibition) in the presence of a MoAb to HLA-DR in each of three coeliac and three control donors studied. Using flow cytometry, increased expression of activation markers (HLA-DR and IL-2R) was demonstrated on gliadin-stimulated T cells from four of nine coeliac patients and three of seven healthy control donors. Cytokines were studied in culture supernatants using ELISA. Gliadin was a potent inducer of IL-6 and IL-10 in 100% of coeliac patients and controls, whereas IL-4 was not produced in either subject group. Gliadin induced IL-2 production in 40% of untreated patients, 42% of treated patients and 35% of healthy control donors. Interferon-gamma (IFN-gamma) in gliadin-stimulated cultures was found only in coeliac patients, observed in 33% of untreated patients and 25% of treated patients. Spontaneous secretion of both IL-2 and IFN-gamma was found more frequently in patients with untreated disease (87% of cases versus 21% of controls for IFN-gamma and 40% versus 0% for IL-2). These results suggest, as manifest by IFN-gamma production, that gliadin stimulates a Th1/Th0-like response in coeliac patients and a Th0-like response in healthy controls.
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PMID:T cell proliferation, MHC class II restriction and cytokine products of gliadin-stimulated peripheral blood mononuclear cells (PBMC). 1044 57

Celiac disease, induced by dietary gluten, is characterized by mucosal atrophy and local inflammation associated with cell infiltration and activation. Unlike other food proteins, gluten and its proteolytic fragments, besides inducing a specific immune response, were shown to activate components of innate immunity and cause, e.g., direct stimulation of TNF-alpha and IL-10 and a significant rise in NO production by peritoneal macrophages. The identity of the active fragments was established by separating the peptic digest of gliadin by RP-HPLC chromatography. The purest fraction with the highest activity was analyzed by mass spectrometry, and the gliadin peptide sequence was identified as VSFQQPQQQYPSSQ. This peptide (T) and its N- and C-terminally shortened forms (A, B, C and D, E, F) were synthesized. Peptide B (FQQPQQQYPSSQ) elicited the highest TNF-alpha, IL-10, and RANTES secretion and increase in IFN-gamma-primed NO production by mouse macrophages. In contrast, C-terminally shortened peptides had a lower ability to stimulate macrophages than the native form.
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PMID:Activation of macrophages by gliadin fragments: isolation and characterization of active peptide. 1192 49

We have investigated the genetic basis of the immune response to dietary gluten in HCD4/DQ8 and HCD4/DQ6 double transgenic mice. Mice were immunized with gluten i.p. or individual peptides s.c. and spleen or draining lymph node T cells were challenged in vitro. Strong proliferative responses to gluten were seen in the HCD4/DQ8 mice, whereas the HCD4/DQ6 mice responded to gluten poorly. A series of overlapping peptides spanning gliadin were synthesized. The HCD4/DQ8 mice reacted to many of the individual peptides of gliadin, while the HCD4/DQ6 mice were relatively unresponsive. T cells isolated from HCD4/DQ8 mice also responded well to modified (deamidated) versions of the gliadin peptides, whereas HCD4DQ6 mice did not. The T cell response to gluten was CD4 dependent and DQ restricted and led to the production of cytokines IL-6, TGF-beta, and IL-10. Finally, intestinal lymphocytes isolated from gluten-fed HCD4/DQ8 mice displayed an activated phenotype. These data suggest that this HLA class II transgenic murine model of gluten sensitivity may provide insight into the initiation of the MHC class II-restricted gluten sensitivity in celiac disease.
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PMID:HLA-DQ determines the response to exogenous wheat proteins: a model of gluten sensitivity in transgenic knockout mice. 1242 37

The mucosal lesion in coeliac disease (CD) is an immune-mediated injury triggered by gliadin and associated with HLA-DQ2 and HLA-DQ8. In view of this, an approach that re-induces tolerance to this antigen should be considered as possible alternative to a strict gluten-free diet in treating CD. However, T-cell activation to multiple antigens, as a consequence of the chemical complexity shown by the antigen gliadin, could hamper the efforts to identify single component(s) useful for tolerance induction. To address this issue, a recombinant alpha-gliadin was tested in tolerance experiments in HLA-DQ8 transgenic mice. As tissue transglutaminase (tTG) treatment of gliadin, previously reported to enhance its stimulatory activity in CD, did not increase its immunogenicity when parenterally administered in these mice, untreated gliadin was used as immunogen. A decrease in systemic T cell responses to the recombinant alpha-gliadin was found after nasal administration of antigen, reflected by lymphocytes proliferation assay. Interestingly, while the immunisation protocol induced transcription of both Th1 (IFN-gamma) and Th2 (IL-4 and IL-10) cytokines, the tolerisation protocol down-regulated significantly only the IFN-gamma mRNA expression. More important, the recombinant alpha-gliadin induced a similar down-regulatory effect in mice immunised with a commercial preparation of wheat gliadin, that is a mixture of many different gliadin components. As the Th1 phenotype and the HLA-DQ8 molecule play a role in the pathogenesis of CD, our data underlined the potential usefulness of this recombinant protein for the immunomodulation of this disease.
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PMID:Intranasal administration of a recombinant alpha-gliadin down-regulates the immune response to wheat gliadin in DQ8 transgenic mice. 1288 Jun 82

Celiac disease (CD) and selective IgA deficiency (IgAD) are frequently associated, and share the same genetic background. The aim of the present study was to evaluate both Type 1 and 2 plasma cytokine levels in CD and in CD-IgAD. IL-2, TNF-alpha, IL-10, IL-4 and IL-13 plasma levels were measured both at diagnosis and after a gluten-free diet (GFD) in 32 CD patients, in 27 CD-IgAD patients and in 30 healthy controls. IFN-gamma levels were significantly higher in CD and CD-IgAD than in controls, TNF-alpha displayed significantly higher levels in CD-IgAD when compared both with controls and with CD, and IL-2 was in CD-IgAD significantly increased respect to controls. Kinetics of the Type 1 cytokine plasma levels did not show a clear relationship with the GFD in both groups of CD patients, and particularly in those with IgAD. IL-4 and IL-13, both at diagnosis and after a GFD, were not significantly different in controls and in celiac patients (with and without IgAD). IL-10, whose production is stimulated by the TNF-alpha, had significantly higher plasma levels in CD-IgAD, but not in CD patients, with a significant decrease after a GFD. CD and especially CD-IgAD patients display persistently higher pro-inflammatory cytokine levels, suggesting a persistent state of activation of pro-phlogistic signals in CD, particularly when IgAD coexists. Serial measurement of serum IL-10 may be an adjunctive evaluating criterion in the follow-up of CD-IgAD patients.
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PMID:Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency. 1505


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