UMLS:C0007570 - FACTA Search

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Query: UMLS:C0007570 (celiac disease)
13,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Involvement of gut immune system has been implicated in the pathogenesis of type 1 diabetes. However, few studies have been performed on the gut mucosa from patients with type 1 diabetes. Thus, we characterized the stage of immune activation in jejunal biopsy samples from 31 children with type 1 diabetes by immunohistochemistry, in situ hybridization, and RT-PCR. We found enhanced expressions of HLA-DR, HLA-DP, and intercellular adhesion molecule-1 by immunohistochemistry even on structurally normal intestine of patients with type 1 diabetes and no signs of celiac disease. In addition, the densities of IL-1 alpha- and IL-4-positive cells detected by immunohistochemistry and IL-4 mRNA-expressing cells evaluated by in situ hybridization were increased in the lamina propria in patients with type 1 diabetes and normal mucosa. Instead, the densities of IL-2, gamma-interferon (IFN-gamma), and tumor necrosis factor alpha-positive cells, the density of IFN-gamma mRNA positive cells, and the amounts of IFN-gamma mRNA detected by RT-PCR correlated with the degree of celiac disease in patients with type 1 diabetes. Our study supports the hypothesis that a link exists between the gut immune system and type 1 diabetes.
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PMID:Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes. 1294 68

A lymphocytic enterocolitis has been reported in a cohort of children with autistic spectrum disorder (ASD) and gastrointestinal (GI) symptoms. This study tested the hypothesis that dysregulated intestinal mucosal immunity with enhanced pro-inflammatory cytokine production is present in these ASD children. Comparison was made with developmentally normal children with, and without, mucosal inflammation. Duodenal and colonic biopsies were obtained from 21 ASD children, and 65 developmentally normal paediatric controls, of which 38 had signs of histological inflammation. Detection of CD3+ lymphocyte staining for spontaneous intracellular TNFalpha, IL-2, IL-4, IFNgamma, and IL-10, was performed by multicolor flow cytometry. Duodenal and colonic mucosal CD3+ lymphocyte counts were elevated in ASD children compared with noninflamed controls (p<0.03). In the duodenum, the proportion of lamina propria (LP) and epithelial CD3(+)TNFalpha+ cells in ASD children was significantly greater compared with noninflamed controls (p<0.002) but not coeliac disease controls. In addition, LP and epithelial CD3(+)IL-2+ and CD3(+)IFNgamma+, and epithelial CD3(+)IL-4+ cells were more numerous in ASD children than in noninflamed controls (p<0.04). In contrast, CD3(+)IL-10+ cells were fewer in ASD children than in noninflamed controls (p<0.05). In the colon, LP CD3(+)TNFalpha+ and CD3(+)IFNgamma+ were more frequent in ASD children than in noninflamed controls (p<0.01). In contrast with Crohn's disease and non-Crohn's colitis, LP and epithelial CD3(+)IL-10+ cells were fewer in ASD children than in nondisease controls (p<0.01). There was a significantly greater proportion of CD3(+)TNFalpha+ cells in colonic mucosa in those ASD children who had no dietary exclusion compared with those on a gluten and/or casein free diet (p<0.05). There is a consistent profile of CD3+ lymphocyte cytokines in the small and large intestinal mucosa of these ASD children, involving increased pro-inflammatory and decreased regulatory activities. The data provide further evidence of a diffuse mucosal immunopathology in some ASD children and the potential for benefit of dietary and immunomodulatory therapies.
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PMID:Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. 1562 51

One of the earliest signs of mucosal immune activation in celiac disease (CD) is an increase in the intraepithelial lymphocyte (IEL) count in the small intestinal epithelium. Though most of those IELs express T cell receptor (TcR)-alphabeta chains, CD is characterized by an increase in TcR-gammadelta+ IELs and by the loss of CD3- IELs. There is currently little evidence that these changes in IEL subset distribution are of relevance in the pathogenesis of CD. We aimed to determine the pattern of cytokine production by IEL subsets isolated from duodenal biopsy specimens from control subjects and CD patients at different stages of the disease. We quantified the capacity of IEL subsets to produce IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-10 by intracellular staining by flow cytometry. All IEL subsets studied displayed a type I cytokine profile in both CD and control subjects, with TcR-alphabeta+ IELs being the main IFN-y producers. Untreated CD exhibited a trend toward a superior accumulation of IFN-gamma per cell but a reduced proportion of INF-gamma+ cells in vitro in association with a significantly increased apoptotic rate of IELs. IL-4 was almost undetectable in all cases and IL-10 showed a tendency to increase in treated and "silent" celiac patients. IEL subsets have a similar Th1 profile in controls and CD patients, and the superior in vitro apoptosis of IELs from CD patients may reflect their superior in vivo activation. The induction of IL-10-dependent regulatory Tr1 responses may be of potential clinical significance in this disease and merits further investigation.
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PMID:Cytokine production by intestinal intraepithelial lymphocyte subsets in celiac disease. 1581 Jun 48

Intestinal intraepithelial lymphocytes (IELs), T-cell receptor alphabeta(+) CD8(+) T cells located between epithelial cells, are thought to contribute to Fas ligand (FL)-mediated epithelial cell death in coeliac disease, a condition characterized by excess interleukin-15 (IL-15). This study evaluates the effects of prolonged IL-15 stimulation on IELs. Human IELs were obtained from jejunal mucosa from gastric bypass operations for morbid obesity and cultured for 3 or 10 days with IL-15. As the culture progressed, an increasing number of IELs became CD94(+) and produced massive quantities of interferon-gamma (IFN-gamma) and IL-10. There was a steady rate of transcription with no feedback regulation. Few chronically activated IELs produced IL-2, IL-4, or tumour necrosis factor-alpha (TauNuF-alpha). To determine whether the accumulation of IL-10 affected IEL functions, endogenous IL-10 was neutralized by antibody during culture with IL-15. This manipulation reduced expression of CD94, NKG2D, and FL as well as FL-mediated killing of Jurkat cells by IELs. It did not affect perforin or TNF-alpha expression or the associated cytotoxic activities. This study shows that IL-15 induces the development of CD94(+) IELs containing IFN-gamma and IL-10, and that endogenous IL-10 promotes FL-mediated cytotoxicity.
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PMID:IL-15 converts human intestinal intraepithelial lymphocytes to CD94 producers of IFN-gamma and IL-10, the latter promoting Fas ligand-mediated cytotoxicity. 1581 4

A delayed and local gastrointestinal hypersensitivity to cow's milk (CM) protein is difficult to diagnose and there are limited data on this disorder. The aim of this study was to investigate local intestinal cytokine secretion in the upper small intestine in children with delayed-type cow's milk allergy (CMA). Duodenal biopsy samples from 31 children with delayed CMA, 14 with celiac disease (CD), and 14 healthy controls were studied for the spontaneous release of IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, and IL-10, measured by cytometric bead array, and of TGF-beta and IL-6 measured by ELISA. The children with delayed CMA secreted more IFN-gamma than the controls (p = 0.006) and the children with CD (p = 0.006). The children with CD secreted more IL-6 compared to the controls (p = 0.008) and the children with delayed CMA (p = 0.002). The children with delayed CMA who had continuously been exposed to CM secreted less TGF-beta than the children with delayed CMA who avoided CM (p = 0.050), and showed a tendency towards lower secretion compared to the controls (p = 0.078). Secretions of TNF-alpha, IL-2, IL-4, IL-5, and IL-10 were low in general; however, the children with delayed CMA who did not avoid CM secreted more IL-4 and IL-10 than the controls (p = 0.016, 0.059). In conclusion, the children with delayed CMA showed up-regulation of IFN-gamma. Interestingly, TGF-beta secretion was up-regulated in those children with delayed CMA who avoided CM suggesting recovery of regulation mechanisms.
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PMID:Increased IFN-gamma secretion from duodenal biopsy samples in delayed-type cow's milk allergy. 1610 38

Twelve patients with T cell large granular lymphocyte leukemia and associated hematocytopenia were treated in a phase I dose-escalation trial with the murine monoclonal antibody Mikbeta1. Mikbeta1 identifies CD122, the beta-subunit shared by the IL-2 and IL-15 receptors. At the doses administered in this study the antibody inhibited the actions of IL-15 on both natural killer and T cells and that of IL-2 when the intermediate-affinity IL-2 receptor was expressed. Mikbeta1 treatment was not associated with significant toxicity or with the development of an immune response to the infused monoclonal antibody. At these doses of Mikbeta1, >95% saturation of the IL-2/IL-15beta receptor (CD122) on the surfaces of the leukemic cells was achieved. Furthermore, in seven patients this led to the down-modulation of the receptor from the surfaces of the leukemic cells. Nevertheless, no patients manifested a reduction in peripheral leukemic cell count or an amelioration of their hematocytopenia. This latter observation may reflect the fact that the monoclonal T cell large granular lymphocyte leukemia leukemic cells of the patients did not produce IL-2 or IL-15 or require their actions for cell survival. In light of the lack of toxicity and lack of immunogenicity of the antibody observed in the present study and the role for IL-15 in the pathogenesis of autoimmune diseases, clinical trials should be performed using the humanized version of Mikbeta1 in groups of patients with human T cell lymphotropic virus I-associated myelopathy/tropical spastic paraparesis, rheumatoid arthritis, multiple sclerosis and refractory celiac disease.
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PMID:Preclinical and phase I clinical trial of blockade of IL-15 using Mikbeta1 monoclonal antibody in T cell large granular lymphocyte leukemia. 1638 51

The interrelationship between prolactin (PRL) and the immune system have been elucitaded in the last decade, opening new important horizons in the field of the immunoendocrinology. PRL is secreted not only by anterior pituitary gland but also by many extrapituitary sites including the immune cells. The endocrine/paracrine PRL has been shown to stimulate the immune cells by binding to PRL receptors. Increased PRL levels, frequently described in autoimmune diseases, could depend on the enhancement of coordinated bi-directional communications between PRL and the immune system observed in these diseases. Hyperprolactinemia has been described in the active phase of some non organ-specific autoimmune diseases, as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and organ-specific autoimmune diseases, as celiac disease, type 1 diabetes mellitus, Addison's disease, autoimmune thyroid diseases. In these diseases PRL increases the syntesis of IFNgamma and IL-2 by Th1 lymphocytes. Moreover, PRL activates Th2 lymphocytes with autoantibody production. Of particular interest is the association between hyperprolactinemia and levels of anti DNA antibodies, islet cell antibodies (ICA), thyreoglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies (ACA), transglutaminase antibodies (tTGAb) in SLE, in type 1 diabetes mellitus, in Hashimoto's thyroiditis, in Addison's disease and in celiac disease, respectively. High levels of PRL have been also frequently detected in patients with lymphocytic hypophysitis (LYH). Several mechanisms have been invoked to explain the hyperprolactinemia in LYH. The PRL increase could be secondary to the inflammatory process of the pituitary gland but, on the other hand, this increase could have a role in enhancing the activity of the immune process in LYH. Moreover, the detection of antipituitary antibodies targeting PRL-secreting cells in some patients with idiopathic hyperprolactinemia suggests the occurrence of a possible silent LYH in these patients. Finally, the role of anti-prolactinemic drugs to inactivate the immune process in LYH is still discussed.
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PMID:Prolactin and autoimmunity. 1641 Oct 65

Celiac disease is caused by sensitivity to wheat gluten in genetically susceptible individuals. The etiological role of the other wheat-related cereals, barley, rye, and oats, is still debated. In order to investigate this issue further, in this study we examined the immune response of celiac mucosal T cell lines to fractions from all four cereals. Cell stimulation was assessed by measuring proliferation (employing (3)H-thymidine incorporation) or cytokine (IL-2, IFN-gamma) production. All five T cell lines demonstrated immunoreactivity to protein fractions from the four related cereals. In some cell lines, reactivity to wheat, barley, and rye was only evident when these cereal fractions had been pretreated with tissue transglutaminase. This study confirms the similar T cell antigenic reactivity of these four related cereals and has implications for their exclusion in the gluten-free diet. However, despite oats stimulation of T cell lines, this cereal does not activate a mucosal lesion in most celiac patients.
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PMID:Intestinal T cell responses to cereal proteins in celiac disease. 1641 36

Celiac disease (CD) results from a permanent intolerance to dietary gluten and is due to a massive T cell-mediated immune response to gliadin, the main component of gluten. In this disease, the regulation of immune responses to dietary gliadin is altered. Herein, we investigated whether IL-10 could modulate anti-gliadin immune responses and whether gliadin-specific type 1 regulatory T (Tr1) cells could be isolated from the intestinal mucosa of CD patients in remission. Short-term T cell lines were generated from jejunal biopsies, either freshly processed or cultured ex vivo with gliadin in the presence or absence of IL-10. Ex vivo stimulation of CD biopsies with gliadin in the presence of IL-10 resulted in suppression of Ag-specific proliferation and cytokine production, indicating that pathogenic T cells are susceptible to IL-10-mediated immune regulation. T cell clones generated from intestinal T cell lines were tested for gliadin specificity by cytokine production and proliferative responses. The majority of gliadin-specific T cell clones had a Th0 cytokine production profile with secretion of IL-2, IL-4, IFN-gamma, and IL-10 and proliferated in response to gliadin. Tr1 cell clones were also isolated. These Tr1 cells were anergic, restricted by DQ2 (a CD-associated HLA), and produced IL-10 and IFN-gamma, but little or no IL-2 or IL-4 upon activation with gliadin or polyclonal stimuli. Importantly, gliadin-specific Tr1 cell clones suppressed proliferation of pathogenic Th0 cells. In conclusion, dietary Ag-specific Tr1 cells are present in the human intestinal mucosa, and strategies to boost their numbers and/or function may offer new therapeutic opportunities to restore gut homeostasis.
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PMID:Gliadin-specific type 1 regulatory T cells from the intestinal mucosa of treated celiac patients inhibit pathogenic T cells. 1695 83

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