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

The state of our understanding of the pathogenesis of DH relies on the integration of several key characteristics: (1) a high frequency of the HLA antigens HLA-B8, HLA-DR3, and HLA-DQw2, (2) an associated GSE, (3) the resolution of both the skin lesions and gut abnormalities in response to a gluten-free diet, and (4) the presence of granular deposits of IgA in normal and perilesional skin. The role of the HLA class II antigens expressed in patients with DH most likely relates to the afferent or initiating arm of the immune system. The association of the HLA-A1, -B8, -DR3, -DQw2 haplotype with Sjogren's syndrome, chronic hepatitis, Graves' disease, and other presumably immunologically mediated diseases, as well as the evidence that some normal HLA-B8, -DR3 individuals have an abnormal in vitro lymphocyte response to wheat protein and mitogens and have abnormal Fc-IgG receptor-mediated functions, suggests that this HLA haplotype or genes linked closely to it may confer a generalized state of immune susceptibility on its carrier, the exact phenotypic expression of which depends on other genetic or environmental determinants. It also is clear, from the association of DH with GSE and the ability to control the cutaneous manifestations of DH with a gluten-free diet, that the gut disease is a critical factor in the pathogenesis of DH. Several pathogenetic theories about the origin of the cutaneous IgA deposits in DH have been proposed, one of which states that the IgA is produced in the gut mucosa as a response to a dietary antigen or gut epithelial antigen and then cross-reacts with the skin of patients with DH. A second hypothesis is that the IgA produced in the gut binds to an antigen and is deposited in skin as an antigen-antibody complex. Finally, it could be that the gut mucosal abnormality simply allows an unknown antigen access to the central immune system where an IgA antibody is produced that binds to skin. The failure to detect circulating IgA anti-basement membrane zone antibodies in patients with DH suggests that either the structures to which the IgA binds are not present in normal skin without DH, that IgA cannot bind to these structures in vitro, or that the circulating IgA is too scant for detection with conventional methods. Finally, it must be considered that the IgA deposited in DH skin may bind as a result of non-antigen-antibody interactions that cannot be duplicated in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dermatitis herpetiformis. 224 67

Celiac disease is defined as a GSE. The small intestinal histological appearance of villous atrophy with crypt hyperplasia, inflammatory cell infiltrate of the lamina propria, and epithelial cell abnormalities is characteristic but not pathognomonic of the disorder. Confirmation of the diagnosis depends on histological improvement when gluten is removed from the diet and deterioration following gluten reintroduction. The pathogenesis of celiac disease appears to require interaction between a number of factors both intrinsic (genetic susceptibility, activation of the immune system) and extrinsic (gluten susceptibility, activation of the immune system) and extrinsic (gluten and possibly other environmental factors). The diagnosis of GSE may be delayed or missed unless the clinician is aware of the broad clinical spectrum of disease presentation. Although celiac disease is widely perceived as a malabsorption syndrome of childhood, the diagnosis is increasingly being made for the first time in adult life. A significant number of patients have no GI symptoms whatsoever. Small intestinal biopsy through the endoscope is the initial and definitive investigation. Most patients show excellent clinical and histological response to a gluten-free diet. The commonest reason for poor response is continuing intentional or inadvertent gluten intake. A minority of patients develop complications, in particular intestinal malignancy, including enteropathy-associated T-cell lymphoma.
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PMID:Diagnosis and treatment of gluten-sensitive enteropathy. 240 97

Celiac disease (gluten-sensitive enteropathy [GSE]) is a disorder characterized by small intestinal mucosal injury caused by dietary exposure to wheat gluten and similar proteins. There is evidence that the mucosal injury is immunologically mediated and there is an inflammatory infiltrate present in the mucosa. It is postulated that release of lipid-derived inflammatory mediators may be involved in the pathogenesis of the mucosal injury. Jejunal mucosal biopsy samples from patients with GSE and from a group of patients who were subsequently shown to have normal jejunal mucosa were incubated with tritiated arachidonate and a peptic/tryptic digest of either gluten or casein. Generation of lipid-derived inflammatory mediators was measured by beta-scintillation counting after separation of metabolites by reverse-phase high performance liquid chromatography with two different buffer systems. The predominant arachidonic acid metabolite generated was 15-hydroxyeicosatetraenoic acid (15-HETE). Mucosa from newly diagnosed GSE patients on a normal diet generated more 15-HETE than either control patients or GSE patients maintained on a gluten-free diet. In addition, gluten acted as a specific stimulus to 15-HETE production by mucosa from the GSE patients on a normal diet. 15-HETE has a number of biologic effects that could contribute to the mucosal changes seen in GSE, and the specific release of 15-HETE by gluten suggests involvement in the pathogenesis of the disorder.
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PMID:Small bowel mucosa from celiac patients generates 15-hydroxyeicosatetraenoic acid (15-HETE) after in vitro challenge with gluten. 309 32

Genetic and environmental factors (breast feeding, probably viral infections) play a role in the expression of the disease. Prevalence of GSE in childhood did not substantially decrease in the last 15 years in all European countries, where GSE is still more common in infantile age and presents frequently gastrointestinal symptoms. A decrease has been reported in childhood in several United Kingdom areas and in Finland, where the clinical presentation is changing, shifting upward with age and coming closer to the adult type of the disease. The following clinical problems have been reported in the recent literature: enamel hypoplasia; monosymptomatic short stature; arthritis and other immunologic diseases; association with diabetes, atopy, Iga deficiency, and probably Down's syndrome. Delay in puberty and other peculiar problems of the disease have been described in adolescents. Tests assessing the permeability of the small intestine and the blood levels of antigliadin antibodies have recently gained success as noninvasive tools for the diagnosis of the GSE. The gluten should be withdrawn from the diet and the challenge with gluten should be performed not before 12 months of gluten-free diet with an accurate timing of the biopsy on the basis of the antigliadin and antireticulin antibodies, to avoid clinical and growth damage. Celiac children do require a permanent gluten-free (and not poor) diet. In reality, too many celiac adolescents are off-diet.
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PMID:Gluten-sensitive enteropathy in childhood. 327 30

Estimates are obtained of the fraction of ingested or inhaled 239+240Pu transferred to blood and tissues of a reproducing herd of beef cattle, individuals of which grazed within fenced enclosures for up to 1064 d under natural conditions with no supplemental feeding at an arid site contaminated 16 y previously with Pu oxide. The estimated (geometric mean [GM]) fraction of Pu transferred from the gastrointestinal tract to blood serum was about 5 x 10(-6) (geometric standard error [GSE] = 1.4) with an approximate upper bound of about 2 x 10(-5). These results are in reasonable agreement with the value of 1 x 10(-5) recommended for human radiation protection purposes by the International Commission on Radiological Protection (ICRP) for insoluble Pu oxides that are free of very small particles. Also, results from a laboratory study by Stanley (St75), in which large doses of 238Pu were orally administered daily to dairy cattle for 19 consecutive days, suggest that aged 239+240Pu at this arid grazing site may not be more biologically available to blood serum than fresh 239+240Pu oxide. The estimated fractions of 239+240Pu transferred from blood serum to tissues of adult grazing cattle were: femur (3.2 X 10(-2), 1.8; GM, GSE), vertebra (1.4 X 10(-1), 1.6), liver (2.3 X 10(-1), 2.0), muscle (1.3 X 10(-1), 1.9), female gonads (7.9 X 10(-5), 1.5), and kidney (1.4 X 10(-3), 1.7). The blood-to-tissue fractional transfers for cattle initially exposed in utero were greater than those exposed only as adults by a factor of about 4 for femur (statistically significant) and of about 2 for other tissues (not significant). The estimated (GM) fraction of inhaled Pu initially deposited in the pulmonary lung was 0.34 (GSE = 1.3) for adults and 0.15 (GSE = 1.3) for cattle initially exposed in utero (a statistically significant difference), which may be compared with the expected fraction of 0.11 at the study site using the ICRP lung model for humans.
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PMID:Transfer of aged Pu to cattle grazing on a contaminated environment. 334 64

Healthy controls and patients with autoimmune chronic active hepatitis (CAH), primary biliary cirrhosis (PBC), coeliac disease (GSE), Crohn's disease (CD) and ulcerative colitis (UC) were examined for serum immunoglobulin A (IgA), secretory IgA (sIgA) and subclasses IgA1 and IgA2 concentrations separately. Elevated secretory IgA levels are found in CAH and PBC. IgA2 level as well as the proportional part of IgA2 out of the serum total IgA are significantly increased in GSE and in CD, while in UC IgA1 levels are significantly decreased as compared to controls. Serial determinations of IgA subclasses may provide a differential diagnostic tool in inflammatory bowel diseases and the findings support the view that increased sIgA levels in CAH and PBC probably have a different origin.
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PMID:Serum secretory IgA, IgA1 and IgA2 subclasses in inflammatory bowel and chronic liver diseases. 361 57

In the present study the relation between the gluten-sensitive intestinal lesion observed in dermatitis herpetiformis (DH) and in gluten-sensitive enteropathy (coeliac sprue) (GSE) was analyzed. Jejunal IgA synthesis in DH was estimated from the extent of incorporation of [(14)C]leucine into IgA in jejunal biopsy specimens during short-term in vitro culture. Patients with DH have significantly elevated incorporation values as compared to normal control individuals (18,880+/-13,614 vs. 5,830+/-3,190 cpm/mg tissue protein/ 90 min) (P < 0.02) and the degree of elevation correlates well with the degree of morphologic abnormality. Thus patients with DH are similar to patients with GSE where elevated local mucosal IgA synthesis has also been observed. By using both morphologic and immunologic criteria for evaluating intestinal status, patients with DH and intestinal disease were distinguished from patients with DH free of intestinal disease. Of the eight patients in the former group, seven carried HL-A8 (87.5%), an incidence which is strikingly similar to that observed in patients with GSE alone (88.5%). In contrast, of the seven patients in the latter group (without gastro-intestinal disease) two had HL-A8, an incidence (27%) not significantly different from that in the normal population (20%) (P > 0.1).Thus, both in respect to local mucosal increase in IgA synthetic rates and in respect to the association with HL-A8, the intestinal lesion of DH is similar to that of GSE.
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PMID:Dermatitis herpetiformis. Immunologic concomitants of small intestinal disease and relationship to histocompatibility antigen HL-A8. 483 85

Fractions and subfractions of gluten were used for intradermal testing in 14 patients with GSE and in 22 control subjects. Twelve out of 14 GSE patients gave positive skin reactions to one or more of the subfractions of gluten. Ten gave a positive reaction between three to eight hours after skin testing; two gave positive tests 20 minutes after injection. Only two out of the 14 had negative skin tests at all times tested. All 22 control subjects were negative to all the subfractions at all times tested. The control subjects consisted of 15 patients with GI disorders other than GSE, three patients with skin disorders other than dermatitis herpetiformis and four healthy controls. Of the three subfractions tested, subfraction B1 appeared most potent in evoking positive skin reactions as judged by the number of GSE patients who responded (11 of 14). Thus, skin testing individuals with this particular portion of gluten subfraction BA may prove to be a useful diagnostic test for GSE.
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PMID:Skin test for gluten-sensitive enteropathy using subfractions of gluten. 644 50

Serologically different teichoic acids could be demonstrated as polysaccharide antigens in staphylococcal species by immunodiffusion (Fig. 1) and counterimmunoelectrophoresis (GSE, Fig. 2). Staphylococcus aureus contained polysaccharide A, S. epidermidis polysaccharide B, S. saprophyticus polysaccharide A beta C, and S. hyicus polysaccharide C (Table 2). These polysaccharides were specific for staphylococcal species and could not be found in micrococci. The antigen preparations for the GSE were autoclaved suspensions of the staphylococcal and micrococcal cultures. The specific antisera (Table 1) were obtained after absorption with pronase-treated staphylococcal reference strains. Treatment with pronase removed protein A from the absorbing staphylococci. In this manner the "nonspecific" loss of specific antibodies was prevented. This would have occurred by the attachment of the Fc-component of immunoglobulin G to protein A of S. aureus. The precipitin-lines contained the polysaccharide-antigens and not protein A.
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PMID:[Demonstration of species-specific teichoic acids in staphylococcal species with reference to protein A activity (author's transl)]. 678 84

Familial occurrence of coeliac disease (gluten-sensitive enteropathy, GSE) is well known, but the mode of inheritance remains unclear. Pena et al proposed that the genetic basis for GSE was due to disease-predisposing alleles at two loci: DRw3 at the HLA-D locus and a GSE-associated B-cell alloantigen at another, unlinked locus. They concluded that clinical disease required one DRw3 (dominant inheritance) and two B-cell alloantigen alleles (recessive inheritance), but the observed gene frequencies were not consistent with the observed disease prevalence. Here we examine the gene frequencies allowed, assuming a 2-locus model, under the constraints of known disease prevalence limits and the segregation ratio calculated from 42 published families. The gene frequencies found by Pena et al predict the segregation ratio observed in the published pedigrees and the best estimates of disease prevalence of GSE, provided 1) a 2-locus model is assumed and 2) both loci exhibit recessive inheritance. The segregation ratio appears incompatible with a 2-locus dominant-recessive model without assuming reduced penetrance.
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PMID:Two locus models for gluten sensitive enteropathy: population genetic considerations. 728 74


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