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

It is now firmly established that dermatitis herpetiformis (DH) is associated with gluten sensitive enteropathy (GSE), although the GSE of DH is generally milder than that form which occurs in celiac disease. The toxic fraction of gluten is in the gliadin, a protein fraction. Gliadin is absorbed in GSE and antigliadin antibodies are present in both DH and celiac disease. There is a question of a cross reactivity between reticulin and gliadin. Gliadin is reported to bind to reticulin. Reticulin has a glycosaminoglycan component. Fibronectin, another component of ground substance, also binds to reticulin. Reticulin and fibronectin are important in basement membrane areas and play a role in basement membrane attachment. Gluten may also exert a lectin effect on gastrointestinal mucosa which contributes to the underlying extracellular matrix. DH and GSE have different pathologies because of their different anatomical sites. The pathomechanisms of both diseases can be explained by one mechanism. Gliadin, or a peptide fraction from it, enters or combines with the extracellular matrix and increases tissue viscosity. The protein fraction of glycosaminoglycans in the extracellular matrix is known to control viscosity. In DH the increased extracellular matrix viscosity would interfere with the diffusion of tissue fluid in the dermal papillae and leads to vesicle formation. The intestinal villi serve a very different function. In GSE the increased extracellular matrix viscosity would decrease adsorption from the intestinal tract producing villi with less volume (shortened or atrophic). The shortened villi decrease the production of digestive enzymes and the absorptive surface. The decreased movement of nutrient tissue fluid supplied to the intestinal epithelial cells also eliminates the microvilli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dermatitis herpetiformis and gluten sensitive enteropathy (including celiac disease)--increased subepithelial extracellular matrix viscosity due to gliadin. 209 Sep 32

It has been shown that GGT activity in the duodenal biopsy homogenates of the children with coeliac disease (n-10) in remission (1 to 3 years of gluten-free diet) is lower than in those with other gastrointestinal tract diseases (n-6). In children with coeliac disease after gluten challenge (1 g of gluten) kg BW for 3 to 6 months) the GGT activity decreased fourfold (n-10). After a few months of gluten challenge there was in coeliac children (n-5) a marked predominance of GGT without sialic acid (the asialic GGT). Similarly there was a prevalence of this form (n-5) in the gut tissue of 3 month old human fetus. In the homogenates of the duodenal bioptates of the children with other gastrointestinal tract diseases (n-6) there was a predominance of the sialic form of the GGT. In the gut tissue of children older than 3 years (n-6) and adults who died of reasons other than gastrointestinal a marked predominance of the sialic form of GGT was found. It has been suggested that presence of asialic form of GGT in coeliac disease is connected with the lectin-like activity of gluten. The process of sialization or desialization takes place within or outside enterocytes. It changes the gut permeability and causes a secondary reaction to the penetrating allergens.
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PMID:[Activity and molecular form of intestinal gamma-glutamyltransferase (GGT) EC 2.3.2.2. in celiac disease]. 257 27

The association of IgA anti-gliadin antibodies and IgA glomerulonephritis (IgA GN) was first reported in 1987 (Am J Nephrol, 1987, 7, 178-183) and has since been confirmed by other groups. We have developed a second generation ELISA (alkaline phosphatase, biotin-avidin) and used it to test 45 adult IgA GN, 34 idiopathic membranous nephropathy (MN), 31 idiopathic nephrotic syndrome (INS), and 11 idiopathic membranoproliferative glomerulonephritis (MPG) patients. IgA anti-gliadin antibodies were found in 24 IgA GN (53%), 1 MN (3%), 1 INS (3%), and 1 MGP (9%) patients. The presence of these antibodies in a patient with proteinuria strongly suggests IgA GN, with a sensitivity of 53%, a specificity of 96%, a positive predictive value of 88% and a negative predictive value of 77%. The presence of IgA anti-gliadin antibodies in IgA GN did not necessarily indicate coeliac disease because: a) neither IgG nor IgA anti-reticulin nor IgA anti-endomysium antibodies were found; b) intestinal absorption tests (folates, EDTA) were normal; c) biopsies of the small intestine were normal; and d) a gluten-free diet did not alter the evolution of the disease. Immunochemical analysis (footprinting after separation of the gliadins by rocket electrophoresis) showed the variability of the fractions recognized by the IgA antibodies from patients and controls, in addition to the absence of a typical profile. Gliadin does not have a lectin effect, since mannan and mannose did not inhibit the ELISA. Immunofluorescent labeling of human kidney with purified rabbit IgG anti-gliadin antibodies did not reveal a common epitope shared by gliadin and renal structures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Significance of IGA antigliadin antibodies during primary glomerulonephritis with mesangial IGA deposits]. 261 Apr 50

A rapid method was developed to diagnose celiac-sprue disease, which was based on the detection of serum antibodies to gluten and simultaneous assessment of the histological structure of the upper small intestinal mucosa. Examinations of labelled lectin binding in the cryostat sections of the small intestinal mucosa, assessment of the status of the regional T-lymphocyte system, and identification of blood autoantibodies to reticuline or epithelial cells of the small intestine provide additional information on the course of the disease. The diagnosis is made within 2-3 hours.
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PMID:[Rapid diagnosis of celiac-sprue syndrome]. 261 Jun 6

The pattern of lectin histochemistry in formalin fixed, paraffin embedded normal jejunal and subtotal villous atrophy specimens from patients with gluten sensitive enteropathy were compared. There was no significant difference in the binding pattern of five lectins (Arachis hypogaea, Canavalia ensiformis, Lens culinaris, Phaseolus vulgaris and Triticum vulgaris) between normal and abnormal specimens. There were significant changes in the binding pattern of three lectins (Dolichos biflorus, Ulex europaeus, Ricinus communis), with special reference to goblet cells staining. These changes were present in all the specimens studied, regardless of the clinical diagnosis of dermatitis herpetiformis or coeliac disease. Dolichos biflorus reactive goblet cells were significantly decreased (p less than 0.001) in abnormal tissue and confined to the luminal edge of the mucosa. Strong reactivity of goblet cells in abnormal tissue was recorded with Ricinus communis and Ulex europaeus, lectins that bind to few or no goblet cells in normal tissue. These findings show that modifications of structural and secretory glycoconjugates occur in the jejunal mucosa of patients with gluten sensitive enteropathy.
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PMID:Evidence of altered structural and secretory glycoconjugates in the jejunal mucosa of patients with gluten sensitive enteropathy and subtotal villous atrophy. 237 37

Increasing experimental evidence suggests that gluten contains a toxic factor that may cause ultrastructural changes in the small intestine which mimic those found in patients with celiac disease. In addition, it has recently been proposed that the toxic factor of gluten is a protein very similar, if not identical, to a well known lectin, wheat germ agglutinin (WGA). Since the cytoskeleton forms the basis of the ultrastructural architecture of the enterocytes the present study was performed to investigate whether WGA has a direct effect on the cytoskeleton in Intestine 407 cells. Changes in the cellular content of filamentous actin (F-actin) in these cells were studied with the fluorescein isothiocyanate (FITC)-phallacidin assay. Cellular exposure to WGA led to a rapid reduction in the cellular content of F-actin (greater than 50%). Intracellular buffering of the cytosolic free calcium level using quin2 as a chelator of calcium totally abolished the WGA-induced reduction in F-actin content. However, increasing the cytosolic free calcium level by exposure to the calcium ionophore ionomycin did not affect the cellular content of F-actin. Ionomycin also failed to potentiate the effect of WGA on the cellular F-actin content. The present results show that WGA changes the organization of the cytoskeleton in Intestine 407 cells via a calcium-dependent mechanism, however, in addition to calcium, some other signal(s), possibly an increased turnover of the phosphatidylinositol cycle, is(are) also required.
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PMID:Effects of wheat germ agglutinin on the cellular content of filamentous actin in Intestine 407 cells. 322 18

Coeliac disease has a known strong linkage with the HLA complex and has also recently been linked to the T cell receptor genes but the mechanism whereby these genes confer susceptibility is not known. This study has examined two possible mechanisms: (i) direct, lectin-like binding of alpha-gliadin (the causative agent of CD) to HLA or TcR molecules and (ii) antigenic cross-reactivity between alpha-gliadin and HLA or TcR molecules. A flow cytometer was used to assess interactions between alpha-gliadin, anti-alpha-gliadin antibodies (raised in both coeliac patients and in rabbits) and EBV-transformed B cell lines from coeliac patients and HLA-matched and mismatched normal controls. The B cell lines were shown to express HLA-DP, -DQ and -DR antigens which are also found on coeliac intestinal epithelial cells. After incubating B cell lines with alpha-gliadin over a wide range of concentrations, no binding of alpha-gliadin to any of the cell lines could be detected with either of the gliadin-specific antibodies. This suggests that HLA molecules do not bind to alpha-gliadin in a lectin-like fashion. In contrast to the B cell lines, alpha-gliadin binding to peripheral blood monocytes could be demonstrated. This binding occurred equally to patient and control monocytes and was not influenced by HLA allotype. The second possibility tested was that alpha-gliadin and the disease-associated HLA molecule bear antigenic similarities. However, neither rabbit anti-gliadin serum nor purified human alpha-gliadin antibody bound directly to the B cell lines. Using peripheral blood T cells similar results were obtained; no binding of alpha-gliadin or antibodies to alpha-gliadin was found. Thus this study shows that the HLA and TcR associations with CD are not explained by the direct binding of alpha-gliadin to these molecules nor by a sharing of antigenic determinants between alpha-gliadin and these molecules.
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PMID:Studies on the interaction between alpha-gliadin and HLA and T cell receptor molecules in coeliac disease. 326 19

To investigate in vitro interactions between gliadin peptide fractions that have been shown to be toxic to celiac small intestinal mucosa in humans and small intestinal microvillus membranes (MVM) from rats during postnatal maturation, MVM were prepared from newborn, 18-day-old preweanling, and adult rats. Partially hydrolyzed gliadin peptide fractions B1-B4, and the pure gliadin peptide B3142 were radioiodinated and used for binding assays. Miniature ultracentrifugation was used for separation of unbound material. Binding of gliadin fractions to MVM was weak and nonspecific in terms of lacking saturation and inhibition. There was no inhibition of binding by mannan. Enzyme pretreatment of MVM (trypsin, neuraminidase, phospholipase C) did not result in any significant change of binding. Compared with peptides prepared from bovine serum albumin as a control, there was no significant difference in binding of gliadin peptide fractions to MVM. Thus, a lectin-like effect of gliadin peptides toward MVM, or the existence of a specific intestinal surface receptor for gliadin peptides appeared improbable. There were, however, consistent maturational changes in MVM binding in that newborn MVM bound more B1-B4 and B3142 compared with adult controls (p less than 0.001). Nonspecific binding of gliadin fractions to MVM might be related to the initiation of nonspecific in vitro effects of gliadin, particularly toward the immature small intestine. The MVM binding model in the rat clearly does not provide a system for studying celiac disease pathogenesis, but it might help clarify basic processes in the interaction between food-derived substances and elements of the gastrointestinal mucosal barrier.
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PMID:Food proteins and maturation of small intestinal microvillus membranes (MVM). II. Binding of gliadin hydrolysate fractions and of the gliadin peptide B3142. 333 72

The interaction between dietary lectins, especially wheat germ agglutinin (WGA), and intestinal cells has been implicated in the pathogenesis of celiac disease. The present study was undertaken to investigate the immediate effects following such an interaction. Direct WGA-stimulation of Intestine 407 cells leads to an immediate rise in the cytosolic-free calcium concentration. The major part of this lectin-induced rise is due to an influx of calcium across the plasma membrane into the cytosol. However, WGA-exposure also results in an immediate mobilization of calcium from intracellular stores, most likely mediated via the simultaneous increase of inositol trisphosphate formation in these cells. The transduction mechanism described for WGA in these intestinal cells is not very sensitive towards pertussis toxin, indicating that if a G-protein is involved, it differs from those of most other systems. The suggested role for WGA in changing the functional and structural properties of intestinal cells might involve increases of inositol phosphate and cytosolic-free calcium levels.
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PMID:Direct effects of wheat germ agglutinin on inositol phosphate formation and cytosolic-free calcium level in intestine 407 cells. 335 Aug 60

The effect of intrapharyngeal infusion and subsequent passage of the lectin concanavalin A through the gastrointestinal tract of neonatal guinea pigs was examined. The lectin, administered at a concentration of 1 mg/ml, caused considerable mucosal damage in the stomach. Subsequent passage of the lectin through the small intestine caused little cellular damage to the mucosa, as judged by light and electron microscopy. Parallel morphometric analyses of the jejunum showed a decrease in mean villus height and an increase in mean crypt depth of 8% after 5 h of lectin administration. A 4.7-fold increase in jejunal crypt cell production rate was observed, accompanied by a statistically significant increase in the number of intraepithelial lymphocytes. These morphologic and kinetic changes were accompanied by a three-fold increase in the urinary lactulose:mannitol excretion ratio, indicative of a loss of mucosal integrity. No systemic antibody response to concanavalin A was demonstrated within 5 h of intragastric infusion of the lectin. Concanavalin A, conjugated with 10 nm colloidal gold particles, was also directly infused into the lumen of the jejunum in vivo. Within 60 min, both villous and crypt epithelial cells contained gold particles, demonstrating the rapid accessibility of crypt cells to the lectin. Intercellular spaces appeared within the villous epithelium, although both junctional complexes and spot desmosomes were retained. The brush border was abnormal with signs of incipient vesicularization. These findings have implications for our understanding of the pathogenesis of childhood coeliac disease and for the vulnerability of the neonatal gut to food proteins.
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PMID:Effect of the lectin concanavalin A on the neonatal guinea pig gastrointestinal mucosa in vivo. 343 Feb 51


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