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PubMed2005

Gluten intolerance: gender- and age-related differences in symptoms.

OBJECTIVE: Gluten intolerance is a common, immunologically mediated disorder with a widely variable clinical presentation that affects genetically predisposed subjects. Women seem to be more frequently affected although data on sex differences are poor. In this study the prevalence of different clinical pictures according to sex and age is analysed in a large series of patients. MATERIAL AND METHODS: A total of 1436 patients with gluten intolerance were retrospectively considered, diagnosed from January 1975 to August 2001 based on compatible small-bowel biopsy and response to a gluten-free diet, plus immunofluorescent detection of granular IgA in papillary derma for dermatitis herpetiformis. The clinical picture at onset (classic, non-classic, silent) and age at diagnosis (< or = 2 years, > 2 and < or = 14 years, > 14 years) was recorded; 362 parents of coeliac probands undergoing a familial screening were also studied. The relations among sex, age class and symptoms were analysed using the chi2 test with Yates's correction. RESULTS: The overall female/male ratio was 2.3:1 but the inter-sex difference was significant only when the diagnosis was made in adulthood where a significant association between iron-deficiency anaemia as manifestation at onset in adult women (34% versus 7%) was found. Low weight, dyspepsia and hypertransaminasaemia were more common in adult men than women (20%, 14% and 7% versus 13%, 3% and 2%, respectively). Dermatitis herpetiformis was present more frequently in men (16% versus 9%). The prevalence of silent cases was 6% in men and 3% in women. Familial screening showed the same prevalence (9.3%) of current coeliac disease in fathers and mothers. CONCLUSIONS: Diagnosis of coeliac disease is more frequent in women but physicians' awareness of sex- and age-related differences in clinical presentation could improve diagnostic performances in men.

Adolescent↗
PubMed1977

[Energy requirements for the synthesis of body proteins during growth as determined in model experiments in rats. 2. Studies with dietary casein and wheat gluten used unsupplemented or supplemented with methionine or lysine].

Rats were used in 7 trials each comprising 9 animals (197 total metabolism trials carried out at an environmental temperature of 30 degree). The animals received casein, casein+methionine, wheat gluten, wheat gluten+lysine as protein sources and were investigated for their nitrogen and energy turnover. The rations fed contained between 10% and 27% protein. Supplementation of the natural proteins with synthetic amino acids positively influenced the growth rate and the rate of N retention. The feeding of wheat gluten as sole protein source induced an absolute depression of the food and energy intake. The rates of tetention of protein and fat energy per animal/day showed opposing trends, in dependence upon the protein levels in the rations. It was found in the trials with casein that the proteins yielded 25%, or 18% of the total energy retention if the rats received low protein rations while the percentage of protein energy retention increased to 49-53%, if the rations contained high protein levels. The rats utilized between 67% and 84% of the metabolizable energy for the turnover of body energy. A negative correlation was found between the levels of energy utilization and protein intake. The energy demends for protein retention were calculated (mean of all trials) to be 1.67 kcal of metabolizable energy while those for fat retention amounted to 1.15 kcal. The energy demands for protein retention were not found to be dependent on the type of protein source used. The maintenance requirements of the rats were 102 kcal of metabolizable energy per kg LM0,75.

Animal Feed↗
PubMed2001

High-protein diets in hyperlipidemia: effect of wheat gluten on serum lipids, uric acid, and renal function.

BACKGROUND: The metabolic effects of diets high in vegetable protein have not been assessed despite much recent interest in the effect of soy proteins in reducing serum cholesterol. OBJECTIVE: We assessed the metabolic effects of diets high in vegetable protein (specifically, wheat gluten) on serum lipids, uric acid concentrations, and renal function. DESIGN: Twenty hyperlipidemic men and women consumed isoenergetic test (high-protein) and control metabolic diets for 1 mo in a randomized crossover design. In the high-protein diet, 11% of the total dietary energy from starch in the control bread was replaced by vegetable protein (wheat gluten), resulting in 27% of total energy from protein compared with 16% in the control diet. In other respects, the 2 diets were identical. RESULTS: Compared with the control, the high-protein diet resulted in lower serum concentrations of triacylglycerol (by 19.2 +/- 5.6%; P = 0.003), uric acid (by 12.7 +/- 2.0%; P < 0.001), and creatinine (by 2.5 +/- 1.1%; P = 0.035) and higher serum concentrations of urea (by 42.2 +/- 5.8%; P < 0.001) and a higher 24-h urinary urea output (by 99.2 +/- 17.2%; P < 0.001). No significant differences were detected in total or HDL cholesterol or in the renal clearance of creatinine. LDL oxidation, assessed as the ratio of conjugated dienes to LDL cholesterol in the LDL fraction, was lower with the high-protein diet (by 10.6 +/- 3.6%; P = 0.009). CONCLUSIONS: High intakes of vegetable protein from gluten may have beneficial effects on cardiovascular disease risk by reducing oxidized LDL, serum triacylglycerol, and uric acid. Further studies are required to assess the longer-term effects on renal function.

Adult↗
PubMed1975

Food intake regulation in the weanling rat: effects of the most limiting essential amino acids of gluten, casein, and zein on the self-selection of protein and energy.

The effects of altering the quality of the dietary protein source on the self-selection of protein and energy by the weanling rat simultaneously offered a choice of two diets differing only in protein concentration were tested. The protein-energy selected was measured when the first limiting amino acid lysine was added to gluten; when lysine, methionine, or the first four limiting amino acids were added to gluten or to casein; or when the nutritional quality of zein was altered by manipulation of the content of tryptophan, lysine, or the four most limiting amino acids. The additions of lysine to gluten caused a decrease in the protein-energy selected and an increase in growth rate of the weanling rat. However, improving the amino acid balance of casein or zein did not have this effect. It was concluded that the selection of protein and energy by weanling rats is not related to the nutritional quality of the protein fed.

Amino Acids, Essential↗
PubMed2002

Thyroid-related autoantibodies and celiac disease: a role for a gluten-free diet?

An association between celiac disease and other autoimmune disorders--such as insulin-dependent diabetes, Addison's disease, systemic lupus erythematous, rheumatoid arthritis, alopecia areata, and autoimmune endocrine diseases--has been described. The aim of this study was to evaluate the prevalence of celiac disease in 100 patients with autoimmune thyroid disease. Moreover, the monitoring of patients with concomitant celiac and autoimmune thyroid diseases, after a gluten-free diet or a gluten-containing diet, can give important insights into the effect of dietary habits in thyroid autoantibodies modulation. In our study, the prevalence of celiac disease in patients with autoimmune thyroid disease was 2%. In these two celiac patients, the serologic markers became undetectable 6 months after beginning a gluten-free diet. However, thyroid autoantibodies did not positively correlate with dietary habits.

Adolescent↗
PubMed1983

Autoradiographic localization of a gluten peptide during organ culture of human duodenal mucosa.

An 125I-labeled subfraction of Frazer's fraction III (molecular weight, 8,000) was added to the culture medium during organ culture of duodenal biopsies from two patients with celiac disease in exacerbation. The isotope-labeled gluten peptide was localized by autoradiography after 6, 12, and 24 h of culture. At 6 h, labeling was located mainly in the basal layers of the biopsies. The tissue was well preserved. After 12 h in culture, the labeling had spread to the lamina propria and the crypts. A few grains were located over enterocytes and desquamated cells. Moderate histological signs of toxicity were observed. After 24 h, there was marked toxic deterioration, comparable to that seen after culture with alpha-gliadin. Labeling had spread throughout the entire section. There seemed to be no specificity of the binding, for the entire section was affected. Culture with the identical gluten fraction, in the radionegative state, produced histological deterioration comparable to that seen after exposure to the isotope-labeled peptide. Gluten peptides are presented to the target cells in a unique way during organ culture, different from in vivo conditions. This may influence the results when the organ culture method is used to investigate the pathogenesis of celiac disease.

Adolescent↗
PubMed1991

Serum IgG and IgA anti-gliadin antibodies as markers of mucosal damage in children with suspected celiac disease upon gluten challenge.

Serum anti-gliadin antibodies (AGAs) of the IgG and IgA isotypes were determined in 17 children (mean age of 5.6 years) by means of an enzyme-linked immunosorbent assay (ELISA). All children were suspected of celiac disease. They had been on dietary treatment for at least 10 months before they were challenged with gluten. Based on jejunal biopsy findings, 10 of the 17 children had to be considered positive. The sensitivity of the measurement of AGA at 6 weeks after gluten challenge was found to be 90% for IgG, 100% for IgA, and 100% for IgG/IgA combined. The specificity for IgG, IgA, and the IgG/IgA combination was 100, 71, and 100%, respectively. Twelve weeks after gluten challenge, the sensitivity as well as the specificity of AGA determination for IgG, IgA, and IgG/IgA were 100%. It is concluded that testing both IgG AGA and IgA AGA in children suspected of celiac disease is valuable in monitoring the course of the diagnostic provocation protocol and that jejunal biopsies can be abolished. This inexpensive tool can be useful in reducing the number of intestinal biopsies.

Adolescent↗
PubMed1994

In vitro toxicity of purified gluten peptides tested by organ culture.

Various subfractions of Frazer fraction III were separated by high-pressure liquid chromatography, and their toxicity in vitro (organ culture) was tested in comparison with alpha-gliadin using duodenal biopsies from 25 patients with active celiac disease and subtotal villous atrophy, 2 patients with partial villous atrophy, and 10 nonceliac controls. One dominating fraction, designated Frazer III-2-VIII, was purified by several steps of rechromatography. It was markedly toxic to duodenal explants from patients with active celiac disease. The mean enterocyte height after culture was 15.9 microns compared with 25.6 microns in gluten-free medium. This difference was statistically significant in all cases except one, in which the lowest concentration (110 micrograms) was used. The in vitro toxicity of Frazer III-2-VIII was comparable with the toxicity of alpha-gliadin in twofold to fivefold higher concentrations. No toxicity could be detected in nonceliac explants (mean enterocyte height, 25.7 vs. 24.9 microns in gluten-free medium). The N-terminal amino acid sequence was (Gln)-Ile-Gln-Val-Phe-Pro-Ser-Gly-Gln-Val-Gln-(Trp)-Pro-Gln-Gln-(Gln)-Gl n-Pro- Phe-Pro. This sequence was not homologous to previously reported sequences of toxic gluten peptides. By use of the SwissProt and GenEMBL databases, it was concluded that the peptide Frazer III-2-VIII is part of the gamma-gliadin fraction.

Adolescent↗
PubMed2001

Quantitative phalangeal bone ultrasound is normal after long-term gluten-free diet in young coeliac patients.

BACKGROUND AND AIMS: To determine bone mass using quantitative phalangeal bone ultrasound in young coeliac patients after a long-term gluten-free diet. SUBJECTS: A total of 99 patients with coeliac disease (CD) (52 girls, mean age 15.5 +/- 9.7 years; 47 boys, mean age 14.4 +/- 8.4 years) and 44 healthy subjects matched for age, weight and height (26 girls, mean age 18.4 +/- 9.9 years; 18 boys, mean age 16.3 +/- 11.2 years) were included in the study. METHODS: Bone status was assessed using an ultrasound device that measures amplitude-dependent speed of sound (Ad-SoS) in metres per second. Measurements were made on the phalanges (II-V) of the non-dominant hand, and an average value was computed. Nutrient intake was assessed using a 7-day record. RESULTS: Analysis of variance (ANOVA) and the unpaired t-test showed that the intake of phosphates (P < 0.05), proteins, fat and carbohydrates (P < 0.005 in all) was higher in patients than in controls. No significant difference in Ad-SoS was found between patients and controls (95% CI -10.9 to 60.6) in the overall group, in girls or boys, or in patients following a gluten-free diet strictly or partially. In the patients, only age (beta 4.01, 95% CI 1.84-6.16, P < 0.0005) and weight (beta 2.62, 95% CI 1.53-3.70, P < 0.0001) showed a significant positive relation with Ad-SoS. CONCLUSIONS: In patients with CD, gluten-free diet and increased nutritional intake were accompanied by normal bone mass values as determined by ultrasound on phalanges.

Adolescent↗
PubMed2003

Affective disorders and quality of life in adult coeliac disease patients on a gluten-free diet.

BACKGROUND: Psychiatric symptoms, common in untreated coeliac disease patients, may improve after gluten withdrawal. AIMS: To estimate the incidence of psychiatric disorders in coeliac disease patients on gluten withdrawal and to evaluate: (1) the psychological weight of a chronic disease that involves a restrictive diet and a limited life style; (2) the acceptance of the disease; (3) the effects of both disease and diet on behaviour and quality of life. PATIENTS AND METHODS: Three groups of 100 patients (coeliac disease patients, diabetic patients and healthy controls, respectively) were assessed by means of a professional semi-structured diagnostic interview based on DSM-IV criteria. This interview, together with specific psychiatric questionnaires, ruled out axis I or II psychopathological disturbances. RESULTS: The modified Self-rating Depression Scale and State and Trait Anxiety Inventory Y2 scores were significantly higher in both coeliac and diabetic patients than in healthy controls. The duration of gluten restriction was related to significantly higher modified Self-rating Depression Scale scores in patients with a more recent diagnosis. Quality of life was poorer in both coeliac and diabetic patients than in healthy controls and significantly correlated with anxiety. The Illness Behaviour Questionnaire showed a high psychological and somatic perception of illness in both coeliac and diabetic patients. Its subscale scores correlated significantly with anxiety and depression symptoms. CONCLUSIONS: In coeliac disease, affective disorders should be ascribed to difficulties in adjusting to the chronic nature of the disease rather than directly to the disease itself, thus giving an indication for preventive liaison psychiatric interventions.

Adult↗
PubMed2004

Quality of life in screen-detected and typical coeliac disease and the effect of excluding dietary gluten.

OBJECTIVE: It is widely recognized that 'asymptomatic' patients with coeliac disease often feel better after commencing a gluten-free diet. The aim of this study was to determine a measure of the quality of life in patients diagnosed as having coeliac disease detected both by screening and those with typical clinical symptoms. METHODS: Quality of life (QoL) was measured using the SF36 questionnaire. This was completed prospectively by all subjects who agreed to undergo duodenal biopsy as a follow-up to a serological screening programme. Seventeen typical coeliac patients who presented clinically also completed the QoL assessment at diagnosis. Both coeliac groups were compared to healthy controls. SF36 questionnaires and coeliac serology were repeated in coeliac patients after 1 year on a gluten-free diet. RESULTS: There were no significant differences between the eight SF36 parameters when the screen-detected coeliac patients were compared to controls, and at 1 year follow-up compared to their baseline data. Two QoL parameters (general health, vitality) improved significantly in the typical coeliac patients at 1 year follow-up compared to their baseline data. General health with reference to 1 year previously significantly improved in typical coeliac patients (3.8 vs 2.2; P = 0.0004) but not screen-detected coeliac patients (2.9 vs 2.4; P = 0.08). CONCLUSIONS: Quality of life in screen-detected coeliac patients did not differ significantly compared to controls. Two of eight QoL parameters improved significantly in typical coeliac patients compared to baseline data. Dietary gluten exclusion in typical coeliac patients led to a significant improvement in health at 1 year follow-up, in contrast to screen-detected coeliac patients.

Celiac Disease↗
PubMed1987

IgA anti-endomysial antibodies in dermatitis herpetiformis: correlation with jejunal morphology, gluten-free diet and anti-gliadin antibodies.

Circulating IgA-class anti-endomysium antibodies (EmA) can be detected by indirect immunofluorescence on monkey oesophagus sections. We found EmA in 22 (76%) of 29 patients with dermatitis herpetiformis (DH) on a normal, gluten-containing diet. The highest frequency (100%) of EmA was observed in patients with sub-total villous atrophy. IgA-class antigliadin antibodies (AGA) were found using an ELISA method in 59% of 29 DH patients and in 86% of those with sub-total villous atrophy. There was a significant correlation between EmA titres and AGA levels in individual patients. Gluten-free diet (GFD) treatment caused a rapid decrease in EmA titres; only three of the 12 patients still showed raised EmA after 6-12 months on a GFD and two of these three had failed to adhere to a strict diet. In contrast, no decrease in EmA titres occurred in four patients maintained on a normal diet, and two of the three patients with initially negative EmA developed positive titres when continuing on a normal diet. These results show that both IgA-class EmA and AGA are good indicators of jejunal damage in DH. The rapid fall of EmA titres after gluten withdrawal indicates that this test is also useful for monitoring a patient's adherence to a GFD.

Adolescent↗
PubMed2005

Gluten-free diet survey: are Americans with coeliac disease consuming recommended amounts of fibre, iron, calcium and grain foods?

OBJECTIVE: This survey was conducted to assess nutrient intakes and food consumption patterns of adults with coeliac disease who adhere to a strict gluten-free diet. DESIGN: Three-day estimated self-reported food records were used to assess daily intakes of calories, percent daily calories from carbohydrates, dietary fibre, iron, calcium and grain food servings. SUBJECTS: Volunteers for this survey were recruited through notices placed in coeliac disease support group newsletters, as well as a national magazine for persons with coeliac disease. Forty-seven volunteers met all criteria for participation and returned useable food records. RESULTS: Group mean daily intake of nutrients by gender: Males (n = 8): 2882 calories; 55% carbohydrate; 24.3 g dietary fibre; 14.7 mg iron; 1288.8 mg calcium; 6.6 grain food servings. Females (n = 39): 1900 calories; 52% carbohydrate; 20.2 g dietary fibre; 11.0 mg iron; 884.7 mg calcium; 4.6 grain food servings. Recommended amounts of fibre, iron and calcium were consumed by 46, 44 and 31% of women and 88, 100 and 63% of men, respectively. CONCLUSIONS: Nutrition therapy for coeliac disease has centred around food allowed/not allowed on a gluten-free diet. Emphasis also should be placed on the nutritional quality of the gluten-free diet, particularly as it concerns the iron, calcium and fibre consumption of women. The use of the estimated food record as the dietary survey method may have resulted in the under-reporting of energy intake. Due to the small sample size and possible bias of survey participants, the findings of this survey may not be representative of the larger coeliac community.

Adult↗
PubMed1983

HLA-DR3- and HLA-DR7-restricted T-cell hyporesponsiveness to gluten antigen: a clue to the aetiology of coeliac disease?

Coeliac disease (CD) is strongly associated with the human class-II HLA determinants HLA-DR3 and -DR7. We investigated the relative frequency of gluten-reactive T cells from DR3- or DR7-positive. CD patients and healthy controls who were heterozygous at the DR locus. We found a consistently and significantly lower frequency of gluten-reactive T cells when the antigen was presented by monocytes in conjunction with DR3 or DR7 than in conjunction with the other DR determinant of the T-cell donor. In contrast, the frequency of reactive T cells in these donors to other antigens was not reduced in conjunction with DR3 or DR7. These results indicate a specific immunoregulatory function associated with class-II HLA molecules. The reduced frequency of gluten-reactive T cells in association with HLA-DR3 or -DR7 may be directly involved in the development of CD.

Antigens↗
PubMed1983

T-lymphocyte activation by a gluten fraction, glyc-gli. Studies of adult coeliac patients and healthy controls.

A gluten fraction (glyc-gli) induced proliferation of T lymphocytes obtained from coeliac patients or healthy controls. Glyc-gli acted as an antigen, and T-cell activation was strongly dependent on antigen-presenting monocytes in the cultures. The lymphocyte response was similar for HLA-B8/DR3-positive and HLA-B8/DR3-negative healthy controls, and coeliac patients in remission on a gluten-free diet could not be distinguished from the controls by the degree of proliferative activity in this test. Conversely, untreated coeliac patients showed a significantly lower lymphocyte response to glyc-gli than both coeliac patients in remission and controls. This result may reflect sequestration of gluten-specific cells into the mucosal lesion or mesenteric lymph nodes in patients with active coeliac disease.

Adolescent↗
PubMedDate not supplied

Recovery of the small intestine in coeliac disease on a gluten-free diet: changes in intestinal permeability, small bowel morphology and T-cell activity.

Intestinal permeability was assessed before and 1, 2, 4, 8 and 12 weeks after commencing a gluten-free diet (GFD) in eight coeliac subjects. Intestinal morphology was quantified in six coeliac subjects on a normal diet, six coeliac subjects on a GFD, and 21 normal subjects. T-cell activity was measured in the eight coeliac subjects by soluble interleukin-2 receptor (sIL-2R) concentration (normal less than 477 U/mL). Intestinal permeability was increased 10-fold with a geometric mean value of 0.72 on a normal diet, and decreased to 0.17 at 4 weeks (P = 0.04), to 0.07 at 8 weeks (P = 0.010), and to 0.20 at 12 weeks (P = 0.015) of a GFD. Two of the eight subjects showed a poor response to gluten withdrawal. Quantitative intestinal morphology showed no significant improvement after 3 to 6 months of a GFD. Mean +/- s.d. sIL-2R concentrations in the eight subjects were increased 5-fold higher than control values at 1400 +/- 530 U/mL on a normal diet and decreased to 750 +/- 200 U/mL after 12 weeks of a GFD (P = 0.004). We conclude that intestinal permeability improves rapidly in the majority of coeliac subjects after commencing a GFD, although some abnormal permeability and increased T-cell activity persists. This may be due to varying degrees of gluten ingestion resulting in continued immune activation.

Adult↗
PubMed1986

IgA endomysium antibody in children with dermatitis herpetiformis treated with gluten-free diet.

The IgA antibody to endomysium of smooth muscle (IgA-EmA) was measured in 32 children with confirmed dermatitis herpetiformis who were eating gluten-free diets. One patient had IgA-EmA before treatment but had a negative test one month later while on the diet. Two so treated for less than one year still had antibody, but of seven children treated for more than one year with gluten-free diet, none had detectable antibody. It was present in 13 of 20 children not adhering to the prescribed diet. The antibody was absent in 4 children with linear IgA bullous dermatosis and 43 children with various skin and intestinal diseases. These findings correspond to those in adults with dermatitis herpetiformis and indicate that IgA-EmA is also a marker for gluten-sensitive enteropathy in children.

Child↗
PubMed2000

Gluten sensitivity in monozygous twins: a long-term follow-up of five pairs.

OBJECTIVE: The aim of this study was to investigate the role of genetic factors and the characteristics of five monozygous twin pairs with at least one member affected by gluten sensitivity. METHODS: Five pairs of monozygous female twins, of whom one or both were affected by gluten sensitivity (i.e., celiac disease or dermatitis herpetiformis), were followed-up for 11-23 yr. RESULTS: Three pairs were concordant for celiac disease: the onset was comparable and synchronous in two pairs; in the third, one member presented an overt malabsorption syndrome, and the other developed iron deficiency anemia 10 yr later. Discordance for gluten sensitivity was found in the remaining two pairs, one of whose members was diagnosed as having, respectively, celiac disease and dermatitis herpetiformis. CONCLUSIONS: As no environmental factors were found to affect the phenotypic expression of the disease, genetic factors seem to play a major role. The presence of overt or latent celiac disease in three of the four siblings of the three concordant twins, and the association with cystic fibrosis in all three siblings of one of these families, further supports this hypothesis.

Adult↗