Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Celiac disease is characterized by small intestinal damage with loss of absorptive villi and hyperplasia of the crypts, typically leading to malabsorption. In addition to nutrient deficiencies, prolonged celiac disease is associated with an increased risk for malignancy, especially intestinal T-cell lymphoma. Celiac disease is precipitated by ingestion of the protein gliadin, a component of wheat gluten, and usually resolves on its withdrawal. Gliadin initiates mucosal damage which involves an immunological process in individuals with a genetic predisposition. However, the mechanism responsible for the small intestinal damage characteristic of celiac disease is still under debate. Small intestinal biopsy with the demonstration of a flat mucosa which is reversed on a gluten-free diet is considered the main approach for diagnosis of classical celiac disease. In addition, IgA antibodies against gliadin and endomysium, a structure of the smooth muscle connective tissue, are valuable tools for the detection of patients with celiac disease and for therapy control. Incidence rates of childhood celiac disease range from 1:300 in Western Ireland to 1:4700 in other European countries, and subclinical cases detected by serological screening revealed prevalences of 3.3 and 4 per 1000 in Italy and the USA, respectively. IgA antibodies to endomysium are particularly specific indicators of celiac disease, suggesting that this structure contains one or more target autoantigens that play a role in the pathogenesis of the disease. However, the identification of the endomysial autoantigen(s) has remained elusive. We identified tissue transglutaminase as the unknown endomysial autoantigen. Interestingly, gliadin is a preferred substrate for this enzyme, giving rise to novel antigenic epitopes.
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PMID:Identification of tissue transglutaminase as the autoantigen of celiac disease. 921 95

Our knowledge of celiac disease pathogenesis has recently made rapid progress. The disorder is now considered the result of a complex interplay of intrinsic (genetic) and variable extrinsic (environmental) factors that explain the wide spectrum of clinical manifestations ranging from asymptomatic to severe malabsorption. Gluten peptides are efficiently presented by celiac disease-specific HLA-DQ2- and HLA-DQ8-positive antigen-presenting cells, and thus drive the immune response, predominantly in the connective tissue of the lamina propria. Tissue transglutaminase, which has been identified as the highly specific endomysial autoantigen, is released from cells during inflammation. It may potentiate antigen presentation by HLA-DQ2 and HLA-DQ8 by deamidating or cross-linking gluten peptides. The result is lamina propria T-cell activation and mucosal transformation by activated intestinal fibroblasts. In the future, manipulation of the gut-associated lymphoid tissue may allow reduced sensitivity or even generate oral tolerance to gluten. Long-standing untreated celiac disease, even if clinically silent, predisposes for other autoimmune diseases. Therefore, population screening for immunoglobulin A antibodies to tissue transglutaminase seems justified.
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PMID:Current concepts of celiac disease pathogenesis. 1127 52

Coeliac disease is the most common disorder with malabsorption of the small intestine, caused by the gluten fraction of cereals in genetically predisposed individuals. T-cell mediated autoimmune processes are initiated by gluten exposure, leading to both intestinal and extraintestinal manifestations, therefore coeliac disease is nowadays considered to be a systemic disorder. More and more diseases are proved to be associated with coeliac disease, in these conditions screening is strongly recommended. The studying of the recently explored autoantibodies against tissue transglutaminase brought us further in the understanding of the pathophysiology of coeliac disease. The spreading of reliable serologic methods modified our knowledge on the clinical picture and prevalence of the disease. In case of long-term dietary abuse the most common complications are decreased bone mineral density and development of lymphomas. Sustained glutenfree diet results in clinical and histological restitution, affects the course of associating diseases beneficially and decreases the risk for malignancies.
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PMID:[Celiac disease today: review of the growing knowledge]. 1114 56

Celiac disease (CD) is an intestinal malabsorption characterized by intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and tissue transglutaminase, an autoantigen located in the endomysium. Tissue transglutaminase belongs to the family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. The role of gliadins in eliciting the immune response in CD and how transglutaminase is linked to the primary reaction are still unclear. In this work, we report the production and analysis of six phage Ab libraries from the peripheral and intestinal lymphocytes of three CD patients. We were able to isolate Abs to transglutaminase from all intestinal lymphocytes libraries but not from those obtained from peripheral lymphocytes. This is in contrast to Abs against gliadin, which could be obtained from all libraries, indicating that the humoral response against transglutaminase occurs at the local level, whereas that against gliadin occurs both peripherally and centrally. Abs from all three patients recognized the same transglutaminase epitopes with a bias toward the use of the V(H)5 Ab variable region family. The possible role of these anti-transglutaminase Abs in the onset of CD and associated autoimmune pathologies is discussed.
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PMID:Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease. 1123 68

Celiac disease (CD) is an autoimmune enteropathy characterized by intestinal malabsorption and immunological responses to dietary gliadins and an auto antigen located in the endomysium. The latter has recently been identified as the enzyme tissue transglutaminase (tTG). The linkage between gliadins, tTG and the autoimmune response has still to be clarified. In this work we report the production and analysis of a phage antibody library from the peripheral blood lymphocytes (PLB) of a CD patient. The library contained polyreactive and monoreactive antibodies to alpha-gliadin, to the dietary antigen beta-lactoglobulin, but not to tTG. The majority of the VH regions of the anti-alpha-gliadin antibodies belonged to the VH 4 family. The possibility of exploiting phage display antibodies as tools to study the molecular events associated with CD is discussed.
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PMID:Analyzing the peripheral blood antibody repertoire of a celiac disease patient using phage antibody libraries. 1134 Nov 73

Anti-endomysial autoantibodies are very useful in the diagnosis and monitoring of celiac disease (gluten-sensitive enteropathy) due to their high sensitivity and specificity for that disorder. The recent discovery that the autoantigen responsible for the endomysial pattern is tissue transglutaminase (tTG) has led to the commercial development of automated enzyme immunoassays for quantitation of that autoantibody. These assays are standardized to provide highly accurate and comparable testing between laboratories for anti-tTG autoantibodies. Celiac disease is a common genetic disease in populations of Europe and the United States. It has a spectrum of expression ranging from silent or mild to severe, with resulting malabsorption that produces multiple-organ system effects due to malnutrition. Many cases miss the diagnosis because the symptoms are not classic or the clinical syndrome is not severe. Because the treatment of celiac disease (avoidance of wheat products) is so effective and inexpensive and because celiac disease is so common in selective populations, a highly reliable test for its detection such as anti-tTG should find wide application in clinical practice.
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PMID:Commentary: advances in the laboratory diagnosis of celiac disease. 1134 24

Celiac disease (CD) is a small intestinal disorder with overt malabsorption in the minority and with subclinical or atypical symptoms in the majority of patients. It is triggered by gluten and related cereal proteins in a unique genetic background (HLA-DQ2 or DQ8 and other unmapped genes). CD is characterized by a highly specific mucosal autoantibody response to tissue transglutaminase. In the intestine this enzyme creates antigenic neoepitopes in gluten peptides which are more efficiently presented to the immune system in the context of HLA-DQ2 or DQ8. Between 3% and 6% of patients with type 1 diabetes mellitus (DM) have (atypical) CD, and the prevalence of a variety of autoimmune diseases in patients with CD correlates with the time of gluten exposure, reaching 35% after 20 years. It is still unknown whether oligosymptomatic CD favors the development of type 1 DM and whether a gluten-free diet modifies the progression of DM in general. Apart from shared or adjacent HLA loci in both diseases, post-translational modification of potential autoantigens by enzymes such as tissue transglutaminase could play a role in the autoimmunity of type 1 DM.
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PMID:Celiac disease and its link to type 1 diabetes mellitus. 1139 50

Coeliac disease is the most common disorder with malabsorption of the small instestine, caused by the gluten fraction of cereals in genetically predisposed individuals. Gluten peptides are efficiently presented by coeliac disease-specific HLA-DQ2- and HLA-DQ8-positive antigen-presenting cells, and thus drive the antigen-presenting cells, predominantly in the connective tissue of the lamina propria. The studying of the recently explored autoantibodies against tissue transglutaminase brought us further in the understanding of the pathophysiology of coeliac disease. The spreading of reliable serologic methods modified our knowledge on the clinical picture and prevalence of the disease. Long-standing untreated coeliac disease, even if clinically silent, predisposes for other autoimmune diseases. Therefore, population screening for immunoglobulin A antibodies to tissue transglutaminase seems justified.
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PMID:Genetic associations and immunopathogenesis of coeliac disease. 1173 88

Serology markers of coeliac disease (CD) - antigliadin IgA/IgG antibodies (AGA/AGG) with purified alpha-gliadin, antiendomysium IgA antibodies (EmA) and anti-tissue transglutaminase (atTG) IgA/IgG antibodies--determined in 1451 serum samples, were analysed with respect to different screening algorithms. Determination of atTG using five ELISA methods was compared taking into account the impact of human recombinant antigen and IgG class of atTG. A subgroup of 119 patients undergoing small intestinal biopsy was used to calculate sensitivity and specificity of CD markers. The highest sensitivity (94%) was obtained for AGG, and the highest specificity (93.5%) was obtained for EmA. All coeliac disease patients were detected using the combination of all four CD markers, resulting in 100% sensitivity. CD and type 1 diabetes mellitus autoantigens were determined in 139 diabetic patients. The atTG IgA mean value (16.7 IU/ml) was higher in the antiglutamate dehydrogenase antibody (GAD)-positive subgroup, where at least one CD marker was positive in 83.6% subjects. In the GAD-negative subgroup atTG IgA was 8.73 lU/ml and at least one CD marker was positive in 57.4% subjects. atTG in IgA and IgG classes could be recommended as valuable serological markers of CD in the differential diagnosis of malabsorption as well as in various screening algorithms. ELISA determination of atTG with human antigen could increase the specificity, especially in patients with other autoimmune diseases.
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PMID:Tissue transglutaminase-serology markers for coeliac disease. 1211 93

Celiac disease is an intestinal malabsorption characterized by an intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and an autoantigen located in the endomysium. The latter has been identified as the enzyme tissue transglutaminase which belongs to a family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. In a recent paper, we described the selection and characterization of anti-transglutaminase Igs from phage antibody libraries created from intestinal lymphocytes from celiac disease patients. In this work, using transglutaminase gene fragments, we identify a region of tissue transglutaminase recognized by these antibodies as being conformational and located in the core domain of the enzyme. This is identical to the region recognized by anti-transglutaminase Igs found in the serum of celiac disease patients.
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PMID:The analysis of the fine specificity of celiac disease antibodies using tissue transglutaminase fragments. 1239 49


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