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)

Coeliac disease (CD) is a malabsorption syndrome mediated by gluten toxicity. In almost all populations studied CD is strongly associated with HLA.DR3 and to a lesser extent with DR7, the frequency of DR2 is often low. There is a highly significant excess of DR3/DR7 heterozygotes. Although the association of CD with HLA has been known for 15 years the mode of transmission is poorly understood. In multiple case families the segregation of haplotypes is in favour of a recessive mode of inheritance with low penetrance. The rare cases of CD negative for DR3 and DR7 are positive for DR4 and negative for DQw2, ruling out the intervention of DQw2 by linkage disequilibrium. A recent study tends to show an hyporesponsiveness of T lymphocytes from patients to an antigenic extract of gluten.
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PMID:[Celiac disease]. 309 56

The sprue syndromes, tropical and nontropical sprue, were both described as disease entities in the 1880s and share similar morphological features with varying degrees of villus atrophy of the small intestinal mucosa, and both present clinically with malabsorption. Recent cell kinetic studies of the turnover of the intestinal epithelium in sprue have convincingly demonstrated that the flat mucosa is caused by increased efflux (cell death) with compensatory crypt hyperplasia. The pathogenetic insult in tropical sprue appears to be a persistent overgrowth of the small intestine by enteric pathogens after a bout of turista. The pathogenesis of nontropical sprue is determined by both genetic factors, demonstrated with a strong association with certain HLA haplotypes (B8, DR3, DR7 and DC3) and presumably also environmental events (virus infection?), which render the mucosa susceptible to gluten. The cause of the malabsorption syndrome is multifactorial and results from both intraluminal and cellular events. The digestion of proteins, carbohydrates, and lipids is compromised due to decreased pancreatic and biliary secretion. The absorption of the digestive products is also severely affected due to decreased activity of microvillus enzymes (dipeptidases and disaccharidases) and a presumed reduction in the number of transport carriers. The clinical presentation is identical and the distinction between tropical and nontropical sprue is based on the history (ie, exposure to a tropical environment) and the response to treatment. Tropical sprue is cured by treatment with tetracycline and folic acid, whereas nontropical sprue responds to a gluten-free diet. Nontropical sprue is associated with dermatitis herpetiformis by common genetic and morphological features, and the skin lesions in dermatitis herpetiformis are also responsive to a gluten-free diet. Finally, there appears to be an increased incidence of intestinal malignancies (lymphoma, adenocarcinoma) in nontropical sprue.
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PMID:The sprue syndromes. 390 13

Celiac disease (CD) is a small intestinal disorder characterized by the malabsorption of most nutrients. Disease pathogenesis appears to be associated with immune-mediated pathology. Susceptibility is associated with genes coding for DQw2 class II molecules. In the present report we investigated T cell responses to A-gliadin (AGL), a major alpha-gliadin component known to activate disease. Gliadin-specific lines were generated from a CD patient and a normal donor. Three major points were revealed by the analysis of these T cells: (1) On the basis of mapping experiments using Epstein-Barr virus (EBV) lines and DR-transfected fibroblasts and DR-, DP-, and DQ-specific monoclonal antibodies (mAb), all responses appeared to be DR-restricted. Thus, in contrast to the strong association of disease susceptibility with DQ molecules, no DQ-restricted, gliadin-specific response was detectable. (2) Fine specificity analysis, using a panel of synthetic peptides spanning the entire alpha-gliadin component molecule, revealed that the clones derived from the normal donor were DR53-restricted and AGL 21-40-specific, while clones derived from the CD patient were DR7-restricted and peptide 1-20-specific. (3) Both whole AGL and AGL 1-20 were presented to the patient-derived clones with much higher efficiency by DDR-transfected fibroblasts than by EBV lines. These data suggested that fibroblasts processed this determinant efficiently, while EBV lines were unable to do so. Indeed, analysis of a panel of truncated AGL 1-20 analogs revealed that peptide AGL 1-8, which contained the minimal T cell epitope, was presented with equal efficiency by fixed or irradiated EBV and irradiated DR7-transfected fibroblasts.
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PMID:Peripheral T cell response to A-gliadin in celiac disease: differential processing and presentation capacities of Epstein-Barr-transformed B cells and fibroblasts. 751 Oct 85