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)

Lectins recognize carbohydrate moities of glycoproteins and glycolipids, and can elicit several biological effects, including cell agglutination, cell activation and mitogenesis. According to the gluten-lectin theory, celiac lesions represent a response to a toxic lectin, putatively wheat germ agglutinin (WGA). In this study we compared the serum antibody levels IgA, IgG and IgM to WGA and to gliadin in children under investigation for celiac disease (CD), as compared to reference children. We found that the levels of IgA and IgG to WGA as well as gliadin were significantly higher in celiac children on a gluten-containing diet, compared to children on gluten-free diet and reference children. These findings lend support to the concept that WGA is a biologically significant component of gluten. Since WGA can mimic the effects of epidermal growth factor (EGF) at the cellular level, we hypothesize that the crypt hyperplasia seen in celiac children could be due to a mitogenic response induced by WGA.
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PMID:Elevated levels of serum antibodies to the lectin wheat germ agglutinin in celiac children lend support to the gluten-lectin theory of celiac disease. 758 28

The binding patterns of gliadin and selected lectins to jejunal biopsy specimens obtained from children with total villous atrophy during active celiac disease (CD; 19 patients) and in remission (16 patients) were examined by light microscopy. Three categories of carbohydrate-specific lectins were chosen for the study: those recognizing mannose/glucose residues, those recognizing N-acetyl-glucosamine/glucose (glcNAc/glc) residues, and those recognizing N-acetylgalactosamine/galactose (galNAc/gal) residues. The galNAc/gal lectins, with the exception of phaseolus vulgaris agglutinin variants, presented a typical staining of the luminal surface of the jejunal mucosa obtained from CD patients. However, these lectins displayed no reactivity to jejunal sections of CD patients in remission or control biopsies that included healthy children (25 children) and patients suffering from cow milk protein allergy (10 children). The glcNAc/glc lectin showed a strong preferential recognition of CD jejunal tissue but also bound with less intensity to specimens from patients with cow milk allergies and healthy children. Unlike other galNAc/gal lectins, phaseolus vulgaris agglutinin variants were indistinguishable in their binding patterns to the mucosa of control groups and CD patients in remission and failed to react to CD biopsies. The mannose/glc lectins were not distinctive in their binding patterns. In all cases, lectin binding was specifically inhibited by the lectins' competitive saccharides. Atypical of lectin binding patterns, gliadin reactivity was restricted to intracellular areas of enterocytes and was unique to active CD mucosa. The distinctive binding patterns of lectins and gliadin provide a diagnostic tool to distinguish patients with active CD from those in remission or patients with other intestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivity of gliadin and lectins with celiac intestinal mucosa. 787 84

Oral immunization with gliadin (GLI) can induce immunoglobulin A mesangial deposits (IgA nephropathy [IgAN]) in mice. A role for GLI in human IgAN has been inferred from an association with celiac disease, increased serum anti-GLI IgA in patients with IgAN, and benefit from a gluten-free diet observed in some IgAN patients. These effects might be due to the antigenic or lectinic properties of GLI. The aim of our study was to investigate whether GLI binding to glycosylated residues (ie, lectinic activity) favors binding of GLI to cultured rat mesangial cells, bridging IgA macromolecules. We also sought to determine whether GLI binding alters mesangial cell function. Gliadin binds to rat mesangial cells in the third and fourth passages, as determined by immunofluorescence. Gliadin binding is inhibited by co-incubation with 1 mol/L N-acetyl-D-glucosamine and 1 mol/L alpha-D-mannose, sugars competitive for this lectinic bond. Quantification by biotinylated GLI revealed a significant dose-dependent binding of GLI (P < 0.001) inhibited by N-acetyl-D-glucosamine (P < 0.05). Some saccharolytic enzymes, like invertase, modify the cell surface to decrease GLI binding (P < 0.02). In addition, GLI promoted the binding of purified mouse polymeric IgA to mesangial cells. The binding of GLI to mesangial cells modulates arachidonic acid metabolism by cultured mesangial cells, significantly inhibiting prostaglandin E2 production (P < 0.02), increasing synthesis of thromboxane B2 (P < 0.01) and tumor necrosis factor (P < 0.001), but not interleukin-1 beta. These responses were abrogated by co-incubation with N-acetyl-D-glucosamine and/or pretreatment with invertase. Non-immune binding of an environmental alimentary lectin, GLI, to mesangial cells in culture might favor the binding of IgA and IgAIC to mesangial cells, enhancing both IgA mesangial trapping and in situ IgA deposit formation. This could occur via GLI-specific antibodies or by virtue of the binding of nonspecific IgA on a lectinic basis, or both. Moreover, related changes in eicosanoid synthesis might stimulate mesangial cell growth and mesangial matrix production, together with mesangial cell contraction, contributing to the pathogenesis of IgAN.
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PMID:Functional consequences of the binding of gliadin to cultured rat mesangial cells: bridging immunoglobulin A to cells and modulation of eicosanoid synthesis and altered cytokine production. 831 Oct 90

In an approach to examine the lectin-hypothesis in the pathogenesis of coeliac disease, the presence of lectin-like components in three wheat gluten preparations known to induce coeliac disease, gliadin, Frazer fraction III and an acetic acid/ethanol extract of gluten, was investigated. Lectin-like components in these wheat gluten preparations were traced in binding studies employing a variety of model glycoproteins glycosylated with the different types of N-linked oligosaccharides, i.e., those of the high mannose-, complex- and hybrid-type. Binding affinity of wheat proteins to these glycoproteins was analyzed by affinity dotting and blotting techniques and was compared to that of the well characterized lectins Galanthus nivalis agglutinin, Concanavalin A and wheat germ agglutinin. Though the three wheat gluten preparations exhibited binding reactivity for distinct model glycoproteins, no correlation was found between the type of N-glycosylation of the model glycoproteins and their binding capability to the different wheat gluten preparations. Moreover, binding of the three gluten preparations to the model glycoproteins could not be inhibited by competitive saccharides (methyl-alpha-D-mannopyranoside, N-acetyl-D-glucosamine, mannan). Enzymatic deglycosylation of the ligand glycoproteins with endo-beta-N-acetylglucosaminidase H (Endo H, EC 3.2.1.96) or peptide N-glycosidase F (PNGase F, EC 3.5.1.52) abolished their binding reactivity for the plant lectins, but did not affect binding of the wheat gluten preparations. These results give no evidence for the presence of lectin-like components in wheat gluten preparations and do question the 'lectin hypothesis' of coeliac disease.
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PMID:Studies on the aetiology of coeliac disease: no evidence for lectin-like components in wheat gluten. 831 50

Human angiotensin I-converting enzyme (ACE) exists in intestinal epithelial cells as a membrane-bound (ACEm) and secretory glycoprotein (ACEsec). The electrophoretic mobilities of ACEsec and ACEm on SDS/polyacrylamide gels are similar; the N-deglycosylated ACEsec and ACEm, in contrast, display slight differences in their apparent molecular masses, indicating that the carbohydrate contents of ACEsec and ACEm are different. Moreover, ACEsec is solely N-glycosylated whereas ACEm is N- and O-glycosylated, assessed by lectin binding studies. Spontaneous release of ACEsec is achieved by incubation of brush border membranes at 37 degrees C. Aprotinin, leupeptin and EDTA partly inhibit the generation of ACEsec, strongly suggesting that ACEsec is generated from ACEm by proteolytic cleavage. The expression levels of ACEsec in the intestine may be associated with the differentiation state of mucosal cells. Thus ACEsec is more abundant than ACEm in immature non-epithelial crypt cells of patients with coeliac disease. Well-differentiated epithelial cells, by contrast, contain predominantly ACEm. The variations in the proportions of cleaved ACEsec in differentiated and non-differentiated cells may be due to varying levels of the cleaving protease. Alternatively, because epithelial cell differentiation is accompanied by alterations in the levels of oligosaccharyltransferases, the results suggest a critical role for the glycosylation pattern of ACEm in its susceptibility to the putative cleaving protease.
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PMID:Secretion of human intestinal angiotensin-converting enzyme and its association with the differentiation state of intestinal cells. 864 15

Gliadin-protein interaction and its relationship to the pathogenesis hypotheses of celiac disease was investigated. Wheat germ agglutinin was not immunodetected in gliadin preparations. Peptic-tryptic gliadin digest was used to study the gliadin-protein interactions by crossed immunoelectrophoresis and affinity blotting. Biotinylated gliadin digest interacted with IgG and bovine serum albumin but not with several glycoproteins. Since albumin and IgG light chains are not glycosylated, this interaction is not lectin-like, neither completely immunological because of recognition of the IgG Fc fraction. Immobilized and boiled IgG was not recognized by gliadin digest as a lectin. Gliadin digest fractions from T-gel chromatography reduced the fluorescence intensity of cis-parinaric acid bound to albumin. The gliadin-protein interaction is not lectin-like or completely immunological but hydrophobic. Hydrophobicity of gliadins may contribute to the pathogenic events that result in celiac disease.
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PMID:Hydrophobic interactions between gliadin and proteins and celiac disease. 895 Feb 94

This paper presents a new hypothesis for the etiology and pathogenesis of celiac disease (CD). It is our contention that CD is triggered by the binding of one or more gliadin peptides to CD-associated HLA class II molecules. Furthermore, we propose that these putative CD peptides bind to oligosaccharide residues on HLA class II molecules distal to the peptide-binding groove invoking recognition and binding by specialized subsets of gamma delta T cell receptor-bearing lymphocytes. The binding of these gamma delta T cells serves as a signal for abrogation of oral tolerance to ingested proteins setting in motion a series of immune responses directed against the small intestinal epithelium of CD patients. CD patients are victimized by this self-distructed immune response because of inheritance of certain combinations of HLA-DQ and DR haplotypes. Dimers encoded by HLA-DR haplotypes may be the primary restriction elements for lectin-like, gliadin peptides while the degree of immune suppression (or lack thereof) to ingested gliadins is governed by inherited HLA-DQ haplotypes. Finally, we speculate that molecular mimicry between one or more gliadin peptides and some, as yet unidentified, bacterial or viral superantigen plays a role in disease pathogenesis.
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PMID:Is celiac disease due to molecular mimicry between gliadin peptide-HLA class II molecule-T cell interactions and those of some unidentified superantigen? 936 19

Levels of secretory IgA1 (SIgA1) in the saliva have not been measured previously in either coeliac disease (CD) or inflammatory bowel disease (IBD). Saliva was collected from coeliacs, IBD patients and controls. The concentration of total SIgA in saliva was measured by enzyme linked immunosorbent assay (ELISA) with an anti-human SIgA antibody as the bound phase and human SIgA isolated from colostrum as the standard. The concentration of SIgA1 was determined using an ELISA with a lectin with a high affinity for human SIgA1. The IBD patients have a significantly higher concentration of SIgA1 than the controls. The rate of secretion of saliva and %SIgA1 was significantly lower in coeliacs than in the control and IBD groups. The rate of secretion of SIgA1 was significantly higher in the IBD than in the coeliacs. We describe hitherto unreported levels of SIgA1 in CD and IBD.
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PMID:Salivary SIgA and SIgA 1 in coeliac disease, inflammatory bowel disease and controls. 1009 41

Mannan-binding lectin (MBL) is the central protein in the activation of complement through the lectin pathway. MBL plasma concentration is genetically determined and varies significantly among individuals. Recent findings suggest that MBL is associated with the pathogenesis of celiac disease (CD). In this study, MBL and C-reactive protein (CRP) levels were determined in 101 celiac patients and 120 controls, with the aim to associate with the presence of gluten in the diet, disease severity, and the presence of concomitant autoimmune diseases. MBL concentration was determined by ELISA and CRP by nephelometry, using a high-sensitivity method. EmA-IgA and other autoantibodies were tested by indirect immunofluorescence. Although a significant increase in MBL levels was observed in male patients compared to female (P = 0.024), the absence of any other association suggests that circulating MBL and CRP concentrations are not associated with clinical and autoimmune CD features in Brazilian patients.
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PMID:Serum mannan-binding lectin levels in patients with celiac disease: an analysis of clinical and autoimmune features. 1739 23

Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the major histocompatibility complex (MHC) region has been reported. In addition, non-MHC genes, such as interferon-induced helicase 1 (IFIH1) and c-type lectin domain family 16, member A (CLEC16A), are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.
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PMID:Selective IgA deficiency in autoimmune diseases. 2182 74


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