T cell depletion in untreated adult coeliac disease.
(41/1975)
The proportional and absolute numbers of circulating thymus dependent lymphocytes (T cells) were reduced in untreated patients with coeliac disease but were normal after treatment with a gluten free diet. There was an inverse correlation between circulating T cell numbers and jejunal intraepithelial lymphocytes. This evidence suggests a possible role for T cells in the pathogenesis of coeliac disease and is a further example of disturbed cell mediated immunity in this condition. (+info)
Cyclosporin in the treatment of adults with refractory coeliac disease--an open pilot study.
(42/1975)
AIM: To evaluate the effect of cyclosporin treatment on clinical and histological parameters in adult patients with refractory coeliac disease. METHODS: Thirteen patients were treated with oral cyclosporin for 2 months, aiming at serum levels of 100-200 ng/mL. Seven extended medication intake up to a maximum of 12 months. Before and after treatment, clinical parameters were monitored and small intestinal biopsies taken. Ten of 13 patients were typed for HLA-DQA1 and -DQB1 alleles. RESULTS: Eight of 13 patients responded histologically to cyclosporin treatment. Normalization of villi was demonstrated in five patients, three after prolonged treatment. Eight patients reported a clinical response, of whom six had concomitant histological improvement. No serious side-effects of cyclosporin were noticed. Nine of 10 patients who were immunogenetically typed carried the coeliac disease associated serologic DQ2 markers, one carried neither DQ2 nor DQ8 markers. CONCLUSION: In our study group of 13 adult refractory coeliac disease patients, cyclosporin in therapeutic doses induced a histological improvement in eight patients (61%), in five of whom (38%) normalization of villi was demonstrated. Thus, we believe that cyclosporin is a therapeutic option in refractory coeliac disease, although we could not confirm earlier reports of unconditional successful treatment. (+info)
Body composition in children with celiac disease and the effects of a gluten-free diet: a prospective case-control study.
(43/1975)
BACKGROUND: Celiac disease is the most common cause of malnutrition in children of Western countries. OBJECTIVE: The objective was to measure body composition in children at the time celiac disease was diagnosed and after consumption of a gluten-free diet (GFD). DESIGN: We assessed body composition by dual-energy X-ray absorptiometry in 29 children and adolescents with a mean (+/-SD) age of 9.5 +/- 3.4 y at the time celiac disease was diagnosed and in a subset of 20 patients after 1.2 +/- 0.2 y of a GFD. We also studied 23 patients aged 21.2 +/- 4.6 y who consumed a GFD for 10.6 +/- 4.5 y. Each patient was matched with a healthy control subject of the same age and sex. RESULTS: Untreated patients weighed less than control subjects (P = 0.04). Fat mass and bone mineral content were lower in the patients than in the control subjects (P < 0.01), as was lean mass of the limbs (P = 0.0013). After approximately 1 y of the GFD, there were no significant differences in body-composition values between patients and control subjects. Similarly, body-composition values of celiac disease patients who consumed the GFD long term were comparable with those of healthy subjects. CONCLUSIONS: Remarkable abnormalities in body composition were found in children at the time of diagnosis of celiac disease. Appropriate dietary treatment reverses body-composition abnormalities quickly and the beneficial effects of gluten withdrawal are persistent. Because these results are harder to achieve if celiac disease is first diagnosed in adulthood, efforts to encourage early diagnosis of celiac disease should be made. (+info)
Changes in body composition, substrate oxidation, and resting metabolic rate in adult celiac disease patients after a 1-y gluten-free diet treatment.
(44/1975)
BACKGROUND: The incidence of celiac disease has been on the rise in both Europe and the United States. Celiac disease patients are at high risk of undernutrition because of nutrient malabsorption. OBJECTIVE: The aim of the present study was to evaluate changes in body composition and energy metabolism in a group of patients with celiac disease before and after consumption of a gluten-free diet (GFD). DESIGN: Body composition (by anthropometry and isotopic dilution), resting metabolic rate (RMR), and substrate oxidation rates (by indirect calorimetry) were assessed in 39 adult celiac disease patients (16 men and 23 women) with a mean (+/-SD) age of 29. 9 +/- 7.6 y, weight of 58.3 +/- 6.6 kg, and percentage body fat of 20.1 +/- 6.7%, and in 63 (29 men and 34 women) age- and height-matched control subjects (age: 33.2 +/- 8.1 y; weight: 66.8 +/- 6.6 kg; and percentage body fat: 25.4 +/- 3.7%). Celiac disease patients were studied twice, at diagnosis and 1 y after treatment with a GFD. RESULTS: Before treatment, celiac disease patients had a lower body weight (P < 0.05) and a higher carbohydrate oxidation rate (P < 0.01) than did control subjects. Carbohydrate oxidation rates correlated positively with fecal lipid loss in untreated celiac disease patients (r = 0.80, P < 0.0001). After the GFD, percentage body fat was higher in celiac disease patients than in control subjects (P < 0.01), and lipid intakes tended to be higher than before treatment. CONCLUSIONS: This longitudinal study showed that the GFD treatment significantly increased body fat stores. Untreated patients preferentially utilized carbohydrates as a fuel substrate, probably as a consequence of both lipid malabsorption and a high carbohydrate intake, and lipid utilization increased with the restoration of the intestinal mucosa. (+info)
Depressed cell-mediated immunity in coeliac disease.
(45/1975)
Fourteen coeliac patients on a gluten free diet (GFD) and 10 on a normal diet were studied by lymphocyte transformation in response to PHA to assess the integrity of cell-mediated immunity (CMI). Transformation was depressed in the majority taking a normal diet, with improvement after a GFD. In some patients the depression may have been due to a serum factor, as transformation was more nearly normal when the lymphocytes were cultured in pooled AB serum than in their own serum. There was no correlation between transformation and nutritional deficiencies. Mantoux tests were performed in some of these and other coeliac patients and there was a very significant reduction in the incidence of positive tests compared with controls. These findings provide evidence of depressed CMI in coeliac patients taking a normal diet with improvement on a GFD and may be of relevance to the high risk of malignancy in coeliac disease, further strengthening the case for a strict GFD. (+info)
Serologic testing for celiac disease in the United States: results of a multilaboratory comparison study.
(46/1975)
The aim of this study was to compare the efficiencies of six reference laboratories for serologic testing for celiac disease. Serum from 20 patients with untreated celiac disease and from 20 controls was thawed, divided, and distributed to each participating laboratory, which performed endomysial antibody tests. Five laboratories also performed antigliadin antibody tests. Sensitivity for endomysial antibody immunoglobulin A (IgA) varied from 57 to 90%. In all laboratories, the specificity for celiac disease was 100%. The sensitivity and specificity for both IgA and IgG antigliadin antibody varied significantly. When results from all three tests were combined in each laboratory, sensitivity was 90 to 100%. The specificity for endomysial antibody was 100% in the laboratories. Sensitivity was less than reported previously. Standardization of these tests is needed in the United States. (+info)
Endomysial antibody in the diagnosis and management of coeliac disease.
(47/1975)
This review determines the significance, usefulness, and application of the endomysial antibody test for coeliac disease in clinical practice. (+info)
Structure of celiac disease-associated HLA-DQ8 and non-associated HLA-DQ9 alleles in complex with two disease-specific epitopes.
(48/1975)
The association of celiac disease (CD) with HLA-DQ2 and HLA-DQ8 is indicative of preferential mucosal T cell recognition of gluten fragments bound to either DQ allele. We have recently identified two gluten-derived, HLA-DQ8-restricted T cell stimulatory peptides, one each from gliadin and glutenin, recognized by specific T cell clones derived from the small intestine of CD patients. We have now performed molecular modeling and examined the fine specificity of these peptides in complex with HLA-DQ8. There is only one binding register for both peptides, with glutamine residues at the p1 and p9 anchor positions. Both T cell clones recognize substituted peptides at p1 and p9, but poorly so at p2-p8, especially the gliadin-specific clone. Contrasting patterns of recognition of p9Gln --> Glu peptide variants (both predicted as better DQ8 binders by modeling) were observed: enhancement of recognition for the gliadin peptide, yet complete absence thereof for the glutenin peptide. The double-substituted gliadin peptide variant p1/9Gln --> Glu, which can also arise by pepsin/acid/transglutaminase treatment, shows a considerable increase in sensitivity of recognition, consistent with better binding of this peptide to DQ8, as predicted by energy minimization. Surprisingly, the two native peptides are also recognized by their respective T cell clones in the context of the related molecule HLA-DQ9 (beta57Asp(+)). The p1/9Gln --> Glu gliadin peptide variant is likewise recognized, albeit with a 10-fold lower sensitivity, the first reported p9Glu binding in a beta57Asp(+) MHC II allele. Our results have important implications for the pathogenesis of autoimmune disease and the possible manipulation of aberrant responses thereof. (+info)