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

Identifying antagonist peptides able to inhibit the abnormal immune response triggered by gliadin peptides in celiac disease (CD) is an alternative therapeutic strategy for CD. The aim of this study was to evaluate the antagonist effect of 10mer, a decapeptide (sequence QQPQDAVQPF) from alcohol-soluble protein fraction of durum wheat, assessing its ability to prevent celiac peripheral blood lymphocytes from activation by gliadin peptides. Peripheral blood mononuclear cells (PBMC) were obtained from DQ2-positive untreated coeliac children and from healthy controls and incubated with the peptic-tryptic digest of bread wheat gliadin (GLP) and peptide 62-75 from alpha-gliadin both alone and with 10mer simultaneously. PBMC proliferation, release of pro-inflammatory Th1 cytokines interferon-gamma and tumor necrosis factor-alpha, release of immunoregulatory cytokine IL-10, and analysis of CD25 expression as indexes of lymphocytes activation were carried out. Enhanced lymphocytes activation was seen after exposure to GLP and p62-75, whereas the simultaneous incubation with 10mer inhibits the lymphocytes response. These data indicate that a peptide naturally occurring in durum wheat exerts in vitro an antagonist effect against gliadin toxicity and could have a protective effect in CD disease.
 ...
PMID:A decapeptide from durum wheat prevents celiac peripheral blood lymphocytes from activation by gliadin peptides. 1721 Nov 43

Celiac disease is a gluten-induced T-cell mediated autoimmune process that results in the destruction of the intestinal mucosa and is associated with an expansion of CD8(+) CD103(+) TCRalphabeta intraepithelial lymphocytes (IELs) in the damaged epithelium. The role of this IEL population in the pathology is unknown. The aim of this work was to compare the cytokine profile and the cytotoxicity pattern from CD8(+) IEL clones isolated from celiac (CD) and non-celiac (NCD) biopsies. We report that the number of IL-10 producing CD clones was significantly lower (26%) than that obtained from the NCD sample (62%). Instead, IL-2 was produced by more CD (44%) than NCD clones (26%). Cytotoxicity patterns against intestinal epithelial cell lines suggest different functional subsets of CD8(+) IELs. CD clones capable of high cytotoxicity produced IL-2 whereas most cytotoxic NCD IELs produced IL-10. This clonal analysis indicates that an impaired immune regulation in celiac mucosa may be partially attributed to the low generation of regulatory CD8(+) IELs that produce IL-10.
 ...
PMID:Human intestinal alphabeta IEL clones in celiac disease show reduced IL-10 synthesis and enhanced IL-2 production. 1736 39

In this study DC numbers, phenotype and DC responses to the Toll-like receptor (TLR)-3 ligand, poly I:C, were examined in new-onset Type 1 diabetes (T1D) patients (ND) and in established T1D patients (ED). Absolute blood myeloid DC (MDC) and plasmacytoid DC (PDC) numbers were decreased in ND and ED patients compared to age-matched controls. The decrease in MDC and PDC counts was less evident in patients with a combination of T1D and coeliac disease (CD) or CD alone. The age-dependent decline in blood DC numbers, found in control children, was not evident in ND patients, such that 2-10 years old ND children had similar MDC and PDC numbers to 15-17 years old controls. In ED patients the t-score of MDC and PDC numbers related to the age of diagnosis but not to disease duration. Blood DC in T1D patients were not distinguished from those of controls by the levels of HLA-DR, CD40 and CD86 expression or the percentage of DC expressing cytokines, IL-12, IL-10, IL-6 and TNF-alpha, in responses to poly I:C. If low DC numbers are shown to contribute to the autoimmunity in T1D, interventions aimed to increase DC numbers may mitigate against beta-cell loss.
 ...
PMID:Decreased blood dendritic cell counts in type 1 diabetic children. 1746 56

Dendritic cells (DC) play a pivotal role in shaping the immune response in both physiological and pathological conditions. In peripheral blood at least two subsets, the myeloid and plasmacytoid, have been described as having different T stimulatory functions and a variable degree of maturation. Certainly, antigen presentation plays a crucial role in the pathogenesis of coeliac disease and circulating immune cells are thought to reflect the state of immune response within the gut. Therefore, we aimed to investigate the quantitative and phenotypical modifications of peripheral blood DC, together with their functional properties, in this pathological condition. Blood samples from 11 untreated patients before and after a course of gluten-free diet, 27 treated patients and 14 controls underwent flow-cytometric analysis, while immunomagnetically sorted DC from the CD patients and eight human leucocyte antigen (HLA)-DQ2/8(+) bone marrow donors were used to evaluate maturation status through the CD83 expression, cytokine profile for interleukin (IL)-6, IL-10, IL-12 and interferon (IFN)-alpha by enzyme-linked immunosorbent assay (ELISA), and functional properties by mixed leucocyte reaction before and after pulsing with digested gliadin. We found that in both untreated and treated patients, a significant reduction of the entire DC population, mainly the plasmacytoid subset, in comparison to healthy controls was observed. In active disease, an impaired allogenic lymphocyte reaction and a significant reduction of IFN-alpha production, paralleled by the presence of a more immature status, were also demonstrated. All the latter modifications have been reverted by pulsing DC with digested gliadin.
 ...
PMID:Reduced number and function of peripheral dendritic cells in coeliac disease. 1758 Dec 62

Celiac disease (CD) is a small intestinal enteropathy caused by permanent intolerance to wheat gluten. Active disease is characterized by a prominent cytokine response of intraepithelial lymphocytes (IELs) to gluten-containing diet with concomitant increase in expression of pro-inflammatory IFN-gamma and down-regulatory IL-10 without increase in tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta1 (TGF-beta1). The aim was to understand the local immune reaction by determining which intraepithelial T cell subsets produce the different cytokines. The three major IEL-subsets gammadeltaIELs, CD4(+)alphabetaIELs and CD8(+)alphabetaIELs, as well as CD94(+)CD8(+)alphabetaIELs, selectively expanded in active CD, were retrieved from small intestinal biopsies of children with active CD and controls and analyzed quantitatively for cytokine mRNA expression. In active CD, CD8(+)alphabetaIELs showed a significant increase in expression levels of both IFN-gamma and IL-10. CD8(+)alphabetaIELs were also the IEL subset with highest expression level per cell of both cytokines and constituted the cellular source for almost all IFN-gamma and most IL-10. Expression levels of both cytokines were higher in CD94(-)CD8(+)alphabetaIELs than CD94(+)CD8(+)alphabetaIELs. TNF-alpha levels were only increased in CD4(+)alphabetaIELs, which also showed the highest expression level per cell and constituted the major source of this cytokine. Interestingly, IL-10 was increased also in CD4(+)alphabetaIELs. Cytokine levels were low in gammadeltaIELs. 'Classical' CD94(-)CD8(+)alphabeta T cells within the epithelium are responsible for the excessive production of IFN-gamma, believed to drive the formation of intestinal lesions in active CD. Production of IL-10 may be a common feature of IELs producing pro-inflammatory cytokines, thereby attempting to limit inflammation in an autocrine fashion.
 ...
PMID:Concomitant increase of IL-10 and pro-inflammatory cytokines in intraepithelial lymphocyte subsets in celiac disease. 1766 May 1

Immunoregulatory NK T-cells are deficient in certain autoimmune diseases. The purpose of this study was to investigate any deficiency of immunoregulatory NK T-cells in celiac disease. NK T-cells were identified by flow cytometry with 6B11 and V alpha 24 markers in blood from 18 normal and 12 celiac subjects. Blood mononuclear cells were stimulated with anti-CD3/CD28 antibodies and intracellular cytokines assessed at 4 h in seven normal and eight celiac subjects. V alpha 24/GAPDH mRNA was quantitated in duodenal biopsies by real time PCR in 17 control and 13 celiac subjects. NK T-cells in celiac subjects were reduced to 30% of those in normal subjects. Intracellular IL-4, IL-10 and IL-13 increased significantly by 33-41% in normal subjects, but did not change in celiac subjects. V alpha 24/GAPDH mRNA from celiac subjects was reduced to 5% of levels in control subjects. We conclude that immunoregulatory NK T-cells are deficient in celiac disease.
 ...
PMID:Deficiency of 6B11+ invariant NK T-cells in celiac disease. 1808 Jan 94

The etiology of refractory celiac sprue (RCS) is unclear. In a high proportion of cases, the clonal nature of intestinal intraepithelial lymphocytes (IEL) can be demonstrated and a pathogenetic implication of intestinal IEL has been postulated. The prognosis of this subgroup of RCS is poor, with a high risk to develop an overt lymphoma and uncontrolled malabsorption despite steroid/immunosuppressive therapy. Cases with a relatively indolent clinical course, however, exist and their early diagnosis may be difficult. To gain insight into the pathogenic implication of intestinal IEL in refractory celiac sprue, we have performed an extensive phenotypic and functional characterization of clonal intestinal IEL in a patient with an indolent form of refractory celiac sprue, using multiparametric flow cytometry. The abnormal lymphocyte infiltrate lacked surface membrane expression of CD3/T-cell receptor (TCR) complexes (TCR(-), CD4(-), CD8(-), sCD3(-)), but contained intracellular CD3(epsilon) (CyCD3(+)) and surface CD103(+) and CD7(+). In particular, these cells showed a unique spontaneous ex-vivo cytokine secretion profile with an increased percentage of CD3(-) IEL containing TNF-alpha and IL-10, in the absence of IL-2, IL-4 and IFN-gamma. Altogether our results suggest that flow cytometry immunophenotyping of intestinal IEL, in cases suspected of celiac disease and their complicated forms, could be of great help in the correct diagnosis of RCS and the understanding of the immunopathogenic mechanisms of the disease and their clinical and/or therapeutical implications.
 ...
PMID:Flow cytometric analysis of intestinal intraepithelial lymphocytes in the diagnosis of refractory celiac sprue. 1840 53

Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-beta, interferon (IFN)-gamma, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients. The numbers of FoxP3- and CD25-expressing cells were studied with immunohistochemistry. Enhanced intestinal expressions of FoxP3, IL-10 and IFN-gamma mRNAs were found in active CD when compared with controls (P-values < 0.001, 0.004, <0.001). In potential CD, only the expression of IFN-gamma mRNA was increased. The numbers of FoxP3-expressing cells were higher in active and potential CD (P < 0.001, P = 0.05), and the ratio of FoxP3 mRNA to the number of FoxP3-positive cells was decreased in potential CD when compared with controls (P = 0.007). The ratio of IFN-gamma to FoxP3-specific mRNA was increased in active and potential CD (P = 0.001 and P = 0.002). Patients with T1D had no changes in regulatory T cell markers, but showed increased expression of IL-18 mRNA. The impaired up-regulation of FoxP3 transcripts despite the infiltration of FoxP3-positive cells in potential CD may contribute to the persistence of inflammation. The increased ratio of IFN-gamma to FoxP3 mRNA in active and potential CD suggests an imbalance between regulatory and effector mechanisms. The increased intestinal expression of IL-18 mRNA in patients with T1D adds evidence in favour of the hypothesis that T1D is associated with derangements in the gut immune system.
 ...
PMID:Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes. 1843 1

The objective of the study was to investigate whether immunologic and biochemical events occurring in the course of type 1 diabetes mellitus might play a role in the development of the celiac disease. The study was carried out on 223 children with long-standing diabetes mellitus type 1 (DM1). All the patients had TSH, fT4, fT3, urinary albumin secretion rate, IgA, level of antigliadin antibodies (AGA) IgA and IgG, antitissue transglutaminase IgA antibodies, antiendomysium (EmA) IgA and IgG antibodies and antitireoglobulin antibodies, antithyroid peroxidase antibodies evaluated. Serum TNF-alpha, IL-6, and IL-10 levels were also measured. The group of children with coincident DM1 and celiac disease and without autoimmune thyroiditis was characterized by significantly higher glycosylated hemoglobin, higher serum TNF-alpha, IL-6 but lower serum IL-10 in relation to the remaining diabetic patients. A statistically significant positive correlation was observed between IgA-anti-tTG and serum TNF-alpha (R = 0.28, p = 0.026); between IgG AGA and serum IL-6 (R = 0.31, p = 0.023); and between glycosylated hemoglobin and IgA-anti-tTG (R = 0.21, p = 0.001) and IgA antiendomysium (R = 0.22, p = 0.001). Poor metabolic control, persistent elevated levels of proinflammatory cytokines, and decreased level of antiinflammatory cytokines occurring in the course of type 1 diabetes mellitus might influence the incidence of celiac disease.
 ...
PMID:Immunologic and biochemical factors of coincident celiac disease and type 1 diabetes mellitus in children. 1867 58

The immune system is pivotal in mediating the interactions between host and microbiota that shape the intestinal environment. Intestinal homeostasis arises from a highly dynamic balance between host protective immunity and regulatory mechanisms. This regulation is achieved by a number of cell populations acting through a set of shared regulatory pathways. In this review, we summarize the main lymphocyte subsets controlling immune responsiveness in the gut and their mechanisms of control, which involve maintenance of intestinal barrier function and suppression of chronic inflammation. CD4(+)Foxp3(+) T cells play a nonredundant role in the maintenance of intestinal homeostasis through IL-10- and TGF-beta-dependent mechanisms. Their activity is complemented by other T and B lymphocytes. Because breakdown in immune regulatory networks in the intestine leads to chronic inflammatory diseases of the gut, such as inflammatory bowel disease and celiac disease, regulatory lymphocytes are an attractive target for therapies of intestinal inflammation.
 ...
PMID:Regulatory lymphocytes and intestinal inflammation. 1930 43


<< Previous 1 2 3 4 5 6 Next >>