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Inheritance of gluten-sensitive enteropathy in Irish Setters.

OBJECTIVE: To establish a model for inheritance of gluten-sensitive enteropathy (GSE) in Irish Setters. ANIMALS: 44 dogs of a 6-generation family of Irish Setters with GSE and 7 healthy Irish Setters. PROCEDURE: Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biopsies (all generations) and measurement of small intestinal permeability by use of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overall probability for each of 4 genetic models of inheritance (autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant) accounting for segregation of partial villus atrophy within the entire family was calculated. RESULTS: The autosomal recessive model was most tenable and was 56,250 times more likely to account for segregation of partial villus atrophy than the autosomal dominant model, assuming disease prevalence of 0.8%. Both sex-linked models were untenable. These conclusions were robust to the error attached to estimation of disease prevalence. High intestinal permeability without morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest generations suggested heterogeneity of lesions associated with GSE. CONCLUSIONS: Genetic transmission of GSE is under the control of a single major autosomal recessive locus.

Animals↗

Intestinal supply of amino acids in sheep fed alkaline hydrogen peroxide-treated wheat straw-based diets supplemented with soybean meal or combinations of corn gluten meal and blood meal.

The intestinal supply of amino acids (AA) in sheep fed alkaline hydrogen peroxide-treated wheat straw (AHPWS)-based diets supplemented with soybean meal (SBM) or corn grain plus combinations of corn gluten meal (CGM) and blood meal (BM) was measured in a 5 X 5 latin square. Sheep (avg wt 45 kg) with ruminal, duodenal and ileal cannulas were fed diets containing 65% AHPWS supplemented with the following protein sources: soybean meal (SBM), corn gluten meal (CGM), blood meal (BM), 2/3 CGM:1/3 BM and 1/3 CGM:2/3 BM. Total nitrogen (N) flow at the duodenum was not affected (P greater than .05) by protein source. Flows of bacterial N and AA increased (P less than .05) and flows of nonbacterial N and AA decreased (P less than .05) when wethers were fed SBM vs corn plus other protein sources. When diets contained SBM, quantities of total AA at the duodenum were lower (P less than .05) and the profile of AA supplied to the intestine was altered substantially. Total flows of AA at the duodenum and total quantities of AA disappearing from the small intestine were similar (P greater than .05) for all diets containing BM and CGM, but flows and disappearance of valine, histidine, lysine and arginine increased linearly (P less than .05), whereas flows and disappearance of leucine, isoleucine and methionine decreased linearly (P less than .05) as BM replaced CGM in the diets. Results suggest that quantities of individual AA flowing to the duodenum and disappearing from the intestine of wethers fed AHPWS-based diets can be altered by source of dietary protein. Furthermore, feeding protein sources resistant to ruminal degradation in combination may improve the profile of AA supplied to the intestine.

Amino Acids↗

Study of behavior of rats with gluten-induced enteropathy.

Association of different psychological and neurological disturbances with gluten intake in coeliac patients was repeatedly described. In the present study gluten-induced enteropathy was elicited in rats by prolonged intragastric administration of gliadin from birth to 10 weeks. Various neurological (contact and visual placing reactions, equilibrium on horizontal bar) and behavioral tests (open field and Morris water maze task) were used to assess the possible deficits. No substantial differences were found in the behavior of rats fed with gliadin compared with those fed with bovine serum albumin (control group). The only difference found between control and experimental rats was that gliadin-fed rats showed slightly higher emotionality in the open field test. It is concluded that prolonged application of gliadin to young rats at enteropathy-inducing dosages does not modify their behavior.

Animals↗

Changes in jejunal mucosa after long-term feeding of germfree rats with gluten.

BACKGROUND: Coeliac disease (CD) or gluten-sensitive enteropathy is a chronic gastrointestinal disease of children and adults. An experimental model using inbred germfree rats has been developed to study the effects of intragastric gliadin application on intestinal mucosa. METHODS: AVN strain Wistar rats (inbred F 87)-germfree were used. Gliadin was applied by intragastric probe from birth until day 63 (0.5-5 mg of gliadin per immunization). Intraepithelial lymphocytes (IEL) were separated from the jejunum, and surface marker characterization was performed using flow cytometry. Isolated IEL were labelled with fluorescein isothiocyanate and injected into control jejunal loops. After 1 h and 6 h the abdominal cavity was reopened. The samples of jejunum were fixed. RESULTS: Prolonged application of gliadin led to the shortening of jejunal villi, crypt hyperplasia, increased number of mitoses in the crypt epithelium, and increased number of IEL-characteristic CD8+, RGL-1+, and TcR alpha/beta +. Transfer of IEL separated from rats fed with gliadin into the intestinal loops of untreated rats led to tight junctions in the enterocytes of the intestinal loops. The IEL isolated from controls (albumin-treated) induced no mucosal changes in intestinal loops. CONCLUSION: These data suggest that IEL isolated from gliadin-treated rats transfer mucosal damage and that gluten-induced enteropathy has an autoimmune component.

Animals↗

Hypokalemic myopathy in a patient with gluten-sensitive enteropathy and dermatitis herpetiformis Duhring: a case report.

The case of a 22-year-old patient with symptomatic hypokalemia caused by rhabdomyolysis is presented as a rarely reported complication of gluten-sensitive enteropathy (GSE) and dermatitis herpetiformis Duhring. The patient's myopathy ceased on potassium supplementation and her other complaints resolved while on gluten-free diet. Recovery was otherwise uneventful with a rapid decline in serum CPK level. At the time of her last follow-up a few months later, she was free of symptoms and CPK remained stable. Patients with GSE may present with hypokalemia in association with diarrhea and emesis, and if potassium loss is rapid, rhabdomyolysis may occur.

Adult↗

Natural killer-like T-cell lymphoma of the small intestine with a distinct immunophenotype and lack of association with gluten-sensitive enteropathy.

We report the case of a large natural killer (NK)-like T-cell lymphoma that involved the ileum and displayed a distinct immunophenotype and complex karyotype. The patient exhibited no evidence of gluten-sensitive enteropathy (celiac disease) or any other type of enteropathy as determined by clinical history, endoscopy, and serology for immunoglobulin A (IgA) antiendomysial and IgG antigliadin antibodies. Molecular studies demonstrated a clonal T-cell receptor gamma chain gene rearrangement. Immunophenotype analysis showed expression of intestinal epithelium-homing receptor CD103, CD7, cytoplasmic CD3 epsilon, CD56, and CD16 but no other T- or NK-cell markers. Cytogenetic analysis of the malignant cells revealed multiple chromosomal abnormalities indicative of a biologically advanced, high-grade lymphoma. A novel subset of normal intestinal intraepithelial lymphocytes, bearing a similar phenotype, has been described; moreover, this subset diminishes, rather than expands, in gluten-sensitive enteropathy. This case supports the notion that lymphomas involving the small intestine represent a heterogeneous group of lymphomas with diverse pathogenetic mechanisms.

Antigens, CD↗

[Changes in the liver in glutenic enteropathy].

AIM: To evaluate frequency of clinical manifestations, biochemical and morphological alterations characteristic of liver affection in patients with glutenic enteropathy (GEP) in correlation with GE duration and severity of malabsorption syndrome (MAS). MATERIAL AND METHODS: 116 GEP patients have undergone clinico-laboratory examination, intestinoscopy with biopsy of jejunal mucosa, puncture biopsy of the liver with morphological examination of the specimens, ultrasonography of the liver. In addition, the immune status was assessed and tests for markers of hepatotropic viruses B and C were made. RESULTS: Clinical symptoms, typical for hepatic lesion in GEP patients, such as yellowness of the skin and scleras, palmar erythema, vascular stella and hepatomegaly were found in 7.2% cases. Hyperaminotransferasemia was detected in 48.4% of new cases of celiac disease, in 18.1% of patients on strict aglutenic diet. Aminotransferase hyperactivity detection was associated with severity of MAS. Morphological alterations in the liver in celiac disease are characterized by fat dystrophy, portal and periportal hepatitis, steatohepatitis or fibrosis. Combined therapy of celiac disease including strict aglutenic diet, correction of metabolic disturbances was not always effective in correction of metabolic processes in the liver. In new GEP cases early adequate therapy was most effective. CONCLUSION: The course of glutenic enteropathy is accompanied with clinicomorphological alterations in the liver. This necessitates use of drugs improving liver function.

Adolescent↗

Gluten-sensitive enteropathy and systemic lupus erythematosus.

A patient with systemic lupus erythematosus developed gluten-sensitive enteropathy, or celiac sprue. The patient's histocompatibility antigens included HLA-B8 and HLA-DR3, previously found to have a high frequency in gluten-sensitive enteropathy and possibility increased as well in systemic lupus erythematosus. Such histocompatibility antigens are common to a variety of autoimmune disorders. An immune basis for the association is discussed herein.

Celiac Disease↗

[Amino acid composition of non-absorbed peptide fractions in rat small intestines. III. Feeding of wheat gluten and molasses yeast. Essential amino acid content of feces].

The authors investigated the nitrogen content of different fractions and in particular the aminoacid composition of the trichloroacetic acid (TCA)-precipitable and TCA-soluble peptides in the distal small intestine of rats which had been fed experimental diets (nitrogen-free or containing casein, wheat gluten or molasses yeast as a protein carrier). Parallel with this, they determined in growing rats the nitrogen and amino-acid digestibility of molasses yeast and wheat gluten according to the technique of faecal analysis, and studied the amino-acid composition of the faecal protein. Independently of the dietary protein fed, the peptide fractions of the content of the intestine showed an amino-acid composition that was largely similar to that found in case of nitrogen-free diet. The amino-acid composition of the faecal protein is, independently of the dietary protein given, relatively constant and corresponds approximately to the intestinal loss protein. There is agreement between the amino-acid composition of the TCA-precipitable peptide fractions and those of the corresponding faecal proteins. These components seem to be of endogenous origin.

Amino Acids↗

Arthritis associated with gluten-sensitive enteropathy.

A 15-year-old girl, with synovitis of the knees and ankles for 3 years before a diagnosis of gluten-sensitive enteropathy, is described. The enteropathy was confirmed histologically and on the basis of a clinical response to a gluten-free diet. The arthritis also resolved promptly, suggesting that it was associated with the bowel disorder.

Adolescent↗

Clinical, biochemical and histological abnormalities in adult celiac patients on gluten-free diet.

Twenty-six adult patients with histologically confirmed celiac disease on gluten-free diet after apparent disease remission were reexamined at 4-6 months intervals for a mean period of 55.4 months (range 13-137). Eight patients remained clinically well with normal blood tests. Eighteen patients had clinical or biological abnormalities. Eleven patients reported repeated episodes of meteorism and abdominal pain and/or diarrhea which disappeared in 2 after lactose withdrawal. Iron deficiency and macrocytic anemia were sometimes observed in 5 and 4 patients respectively. Altered plasma calcium, phosphorus and alkaline phosphatase and/or bone densitometry findings were detected in 7 patients. Seventeen patients (12 presenting some of the above findings) agreed to a repeat biopsy: 13 of these showed grade II and 4 grade III abnormalities. Although adult celiac patients may show marked improvement during gluten-free diet, minor clinical disturbances and biochemical abnormalities may still be present.

Adult↗

Gluten enteropathy appearing after gastric surgery.

Four patients with severe malabsorption syndrome precipitated by gastric surgery are described. The clinical features were diarrhea, steatorrhea, and a dramatic weight loss promptly following surgery. Laboratory determinations were consistent with malabsorption syndrome. Small intestinal mucosal biopsy demonstrated villous atrophy and inflammatory cell infiltration. In each instance, a gluten-free diet led to clinical improvement and a return toward normal of the laboratory measures of absorptive function. The appearance of the proximal intestinal mucosal histology improved in 3 cases. These findings indicate that evaluation of small bowel function should be undertaken prior to gastric surgery in patients with a family or past history of celiac disease, or symptomatology suggestive of an absorptive defect. Furthermore, this study emphasizes the importance of adequate evaluation of the small intestine in patients with steatorrhea following gastric surgery. Although malabsorption in the postgastrectomy patient may result from disruption of intraluminal digestive processes, the recognition of a concomitant gluten enteropathy can lead to lifesaving dietary therapy.

Adult↗

Studies of intestinal lymphoid tissue: the cytology and electron microscopy of gluten-sensitive enteropathy, with particular reference to its immunopathology.

Knowledge of the cytology, ultrastructure and histochemistry of the small intestinal mucosa has advanced considerably over the last 20 years, particularly in regard to the changes associated with coeliac disease. Many of the known structural and cytological changes in coeliac mucosa are probably non-specific, and not directly related to its pathogenesis. It seems important to move away from purely descriptive images of mucosal abnormality such as "villous atrophy', and static measurements, such as crypt-villous ratios. Rather, the mucosa should be viewed as a dynamic, three-dimensional structure and evaluated in terms of total villous cell counts, crypt cell production rates, and so on. The organisation of the lamina propria is still poorly documented, and requires further exploration at the ultrastructural level. More thought should be given to the meaning of mucosal permeability and to its structural counterparts. The immunocytopathology of the coeliac lesion is far from understood; it is questionable whether local humoral activity is central to the pathogenesis of the condition. More needs to be learned of the role of T cells, not only in local mucosal reactions, but also in terms of possible regulatory effects on crypt cell kinetics, villous shape and hence mucosal structure. Increased mitotic activity of epithelial lymphocytes in coeliac disease appears to correlate exclusively with gluten-sensitivity and the use of this presumed immunological marker in the histological diagnosis, and thus prediction, of gluten-sensitised individuals is proposed in this paper.

Basement Membrane↗

[Gluten-sensitive enteropathy with intestinal T-cell lymphoma: an unusual cause of in disabling osteomalacia].

We describe a 64-year-old woman with a malignant intestinal T-cell lymphoma who presented four years later with disabling osteomalacia and secondary hyperparathyroidism due to malabsorption. Only two years later, when the patient had developed fatty stools, flatulence and weight loss, diagnosis of gluten-sensitive enteropathy (GSE) was confirmed by small-intestine biopsy. This case report illustrates that in adults GSE can be oligosymptomatic for long periods. In cases of osteomalacia or rare intestinal T-cell lymphoma a detailed history of bowel movements, inspection of stools, quantification of fat excretion in stools and laboratory tests for malabsorption are recommended. Positive antibodies against gliadin, endomysium and reticulin may support the diagnosis of GSE. However, intestinal biopsy is necessary to verify the presence of GSE. In view of the unspecific histological changes, a follow-up biopsy is recommended in oligosymptomatic cases. Serial measurements of antibodies allow supervision of compliance for a diet strictly free of gluten. In addition, lactose containing milk products need to be restricted initially because of secondary lactase deficiency.

Celiac Disease↗

[Metabolic bone disease in a female patient with gluten enteropathy].

A 41-year old female patient with metabolic bone disease is presented. The disease was caused by malabsorption which developed as a result of gluten induced enteropathy. The diagnosis was confirmed by histological finding of the small intestine mucosa and bones. Following gluten-free diet, calcitriol and calcium tablets, the patient started to move independently and the bone mineralisation improved.

Adult↗

Determination of the mycotoxin fumonisins in gluten-free diet (corn-based commodities) in the Czech Republic.

The fumonisins, mycotoxins produced by Fusarium moniliforme, are known to occur worldwide as natural contaminants of corn. They are associated with several animal diseases and are a potential threat to human health. A total of 127 samples of corn-based foods (gluten-free diet) in the Czech Republic were analysed by Ridascreen Fumonisin Fast ELISA methods in years 1995-1996. Eighty eight % of the corn-based foods were found to be positive for fumonisins (FB1, FB2, FB3) and 12% of the examined corn-based foods laid below of a determination limit which was about 9 ng fumonisins/g corn-based foods. The highest fumonisin contamination levels were recorded in extruded corn products containing up to 1,808 micrograms/kg of fumonisins. Levels ranging from < 9 to 1,243 ng/g fumonisins were detected in polenta. Lower levels of fumonisins were found in other commodities, such as corn flour (up to 487 ng/g), corn instant porridge (up to 788 ng/g), and corn pastes (511 ng/g). Intake of fumonisins from several corn-based foods (gluten-free diet) for the population with coeliac disease was estimated. The highest estimate of exposure dose of fumonisins was determined from corn-extruded bread: 3.2 micrograms/person/day (mean of measured values). Daily intake of fumonisins from polenta is expected 2.8 micrograms/person/day (mean). The lower exposure dose of fumonisins we can expect from corn instant porridge, corn postes and other corn products--corn and amaranth biscuit, corn beverage: 0.9, 1.1 and 0.3 micrograms/person/day (mean) respectively.

Celiac Disease↗

Studies in vivo of omega-gliadins in gluten sensitivity (coeliac sprue disease).

1. Highly purified omega-gliadins from wheat were used to challenge gluten-sensitized individuals. Characteristic responses by mucosal CD3(+) and gamma delta+ lymphocytes were demonstrated. Each lymphocyte subset showed an increase within 8-12 h post-challenge, indicating a specific response by the rectal mucosa to this gliadin species.2. Available sequence data for the omega-gliadins and homologous proteins from barley and rye indicate a common repeating octapeptide motif (consensus PQQPFPQQ). The results indicate, therefore, that the octapeptide repeat, or a contained sequence such as PQQP, plays an important role in the mucosal immunopathology of gluten sensitivity.

CD3 Complex↗

Gluten and the small intestine in rheumatoid arthritis.

A study of the small intestine in patients with rheumatoid arthritis was undertaken because it has been suggested that the disease arises secondary to hereditary enteropathy. No abnormality of jejunal mucosa was detected histologically in five patients with arthritis, and studies of bowel function were normal in six patients. No serologic evidence of increased intestinal permeability, as indicated by antimilk or antijejunal cell antibodies, was detected in sera of 17 arthritic patients. Gluten-free diet, claimed to be helpful in treating the disease, proved of no value in a brief, carefully controlled, hospital trial in five patients.

Adult↗