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PubMed1997

The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet.

BACKGROUND & AIMS: The majority of patients with celiac sprue experience diarrhea before diagnosis. There have been no studies of the prevalence or causes of chronic diarrhea in these patients after treatment with a gluten-free diet. METHODS: Seventy-eight patients with celiac sprue (59 women and 19 men) treated with a gluten-free diet for at least 12 months were surveyed about their bowel habits. Those with chronic diarrhea, defined as passage of loose stools three or more times per week for 6 months, underwent an extensive diagnostic evaluation to determine its cause. RESULTS: Sixty-two of the 78 patients (79%) experienced diarrhea before treatment, and 13 (17%) had chronic diarrhea (of lesser severity) after treatment. The causes of diarrhea in 11 patients consenting to this study were microscopic colitis, steatorrhea secondary to exocrine pancreatic insufficiency, dietary lactose or fructose malabsorption, anal sphincter dysfunction causing fecal incontinence, and the irritable bowel syndrome. Only 1 patient had antigliadin antibodies detected in serum or small intestinal villous atrophy. CONCLUSIONS: After treatment of celiac sprue with a gluten-free diet, chronic diarrhea persists in a substantial percentage of patients. Although ongoing gluten ingestion is one possible cause, other causes may be more frequent. Therefore, diagnostic investigation of diarrhea in celiac sprue after treatment seems warranted.

Adult↗
PubMed1997

Role of pancreatic impairment in growth recovery during gluten-free diet in childhood celiac disease.

BACKGROUND & AIMS: Clinical significance and duration of insufficient release of pancreatic enzymes in childhood celiac disease have not been clarified. The aim of this study was to evaluate the role that pancreatic impairment plays in growth recovery and the duration of this impairment. METHODS: Forty-six patients with celiac disease who had a median age of 2.5 years were enrolled. Fecal chymotrypsin level was determined at diagnosis and then every 15 days after the beginning of a gluten-free diet in all patients. RESULTS: At diagnosis, 17 of 46 patients with celiac disease had subnormal fecal chymotrypsin values. During the gluten-free diet, a progressive reduction in the percentage of patients with subnormal fecal chymotrypsin values was observed: 12 of 46 patients after 30 days and 2 of 46 patients after 60 days. Weight increase after 2 months of gluten-free diet was significantly greater in patients with normal fecal chymotrypsin values at diagnosis than in patients with subnormal values, and a positive correlation was found between fecal chymotrypsin at diagnosis and weight increase (r = 0.56). CONCLUSIONS: A small percentage of patients with celiac disease still had subnormal chymotrypsin concentrations after 60 days of gluten-free diet. Fecal chymotrypsin is a predictive index of weight recovery in the first months after diagnosis of celiac disease; it could be used to select patients for enzyme supplementation therapy.

Body Weight↗
PubMed1980

[Cellular sensitization against gluten in coeliac disease (author's transl)].

The leucocyte-adherence inhibition test was used on 24 patients with malabsorption syndrome, results being compared with those from patients with enteritis of other causes, and those with normal gastro-intestinal tract in order to test cellular gluten sensitization. The test makes it possible to distinguish between gluten-induced and non-gluten induced enteritis. There was a significant linear correlation to inflammatory activity as determined by biopsy as well as reduction in villous length and the villi-crypt index. The results suggest a primary T-cell dependent gluten (or gliadin) sensitization in the aetiology of coeliac disease.

Adolescent↗
PubMed2003

Duodenal histology in patients with celiac disease after treatment with a gluten-free diet.

BACKGROUND: The diagnosis of celiac disease requires characteristic histopathologic changes in an intestinal biopsy with clinical improvement in response to a gluten-free diet. Endoscopy with procurement of biopsy specimens is often performed to document response to the diet, but there are little data on the appearance of treated celiac disease. This study examined the endoscopic and histopathologic appearance of the duodenum of patients with celiac disease whose diet was gluten-free. METHODS: A cohort of 39 adult patients (mean age 52 years, range 20-74 years) with biopsy-proven celiac disease was retrospectively reviewed. All had responded clinically to a gluten-free diet that they had maintained for a mean of 8.5 years (range 1-45 years). The endoscopic and histopathologic appearances of the duodenal mucosa were reviewed. Blinded review of the diagnostic (initial) and post-treatment biopsy specimens was also performed to assess response of individual patients to the diet. RESULTS: The endoscopic appearance was normal in 23%, reduced duodenal folds were present in 46%, scalloping of folds in 33%, mucosal fissures in 44%, and nodularity in 33%. There was more than 1 abnormality present in 46%. Histology was normal in only 21%. The remainder had villous atrophy (69% partial, 10% total). Paired (diagnostic and follow-up) biopsy specimens were reviewed blindly for 12 patients. The mean (SD) intraepithelial lymphocyte count fell from 61 (22) to 38 (17) (normal <30 per 100 epithelial cells) and the crypt-to-villous ratio improved although it did not normalize. CONCLUSIONS: Despite a good clinical response, abnormal endoscopic and histopathologic appearances persist in the majority of patients with celiac disease treated with a gluten-free diet.

Adult↗
PubMed2003

Gluten-free diet in psoriasis patients with antibodies to gliadin results in decreased expression of tissue transglutaminase and fewer Ki67+ cells in the dermis.

Previous studies have shown that 16% of patients with psoriasis vulgaris have IgA and/or IgG antibodies to gliadin, but few have antibodies to endomysium. The increase in duodenal intraepithelial lymphocytes was mild. Still, highly significant clinical improvement was observed after 3 months on a gluten-free diet. This study surveys certain immunohistological aspects of involved and non-involved skin in 28 AGA-positive psoriasis patients before and after 3 months of a gluten-free diet. Staining was performed for CD4+ T lymphocytes, Langerhans' cells, endothelium, proliferating (Ki67) cells and tissue transglutaminase. In the entire group of patients, as well as in those on a gluten-free diet as the only treatment, Ki67 + cells in involved dermis were highly significantly decreased after the diet. There was a significant decrease in Ki67 + cells even in patients without increased intraepithelial lymphocytes. Tissue transglutaminase was highly overexpressed in involved skin in the papillary endothelium, and decreased by 50% after gluten-free diet. The possible role of tissue transglutaminase in the pathogenesis of psoriasis needs further investigation.

Adolescent↗
PubMed2004

Introduction of food during the infant's first year: a study with emphasis on introduction of gluten and of egg, fish and peanut in allergy-risk families.

AIM: The aim of the current study was to retrospectively examine introduction of food during the first year in a representative sample of Swedish children. A secondary aim was to study how parents with history of atopy introduced food to their infants. METHODS: Data derive from 467 infants who visited child health centres in three different counties in Sweden for health check-up at 12 mo of age. The parents were asked to fill in a questionnaire about breastfeeding and/or formula feeding, time of introduction of weaning food focusing on cow's milk, follow-on formula, porridge, fish and egg. Questions regarding hypersensitivity in the family, peanut consumption of mother as well as in the child, and questions about number of siblings, ethnic background and parental education were included. RESULTS: Compliance with suggested introduction of gluten-containing food was low; as many as 45% had avoided gluten until 6 mo of age, instead of introducing gluten between 4 and 6 mo. Only 33% of parents with stated family hypersensitivity avoided giving their child fish and 23% avoided egg during the first year, even though this recommendation was present at the time of the study. Almost 50% of all mothers had avoided peanuts during pregnancy even though there was no such advice. The avoidance of peanut was not connected to hypersensitivity in the family. CONCLUSION: These results suggest that time of introduction of gluten was not in accordance with the current recommendation. The results imply that there is a need to follow up if and how this feeding information is distributed to parents with infants and also to sharpen the information to the right target groups, otherwise implementation of preventive strategies will be less useful.

Age Factors↗
PubMed1998

Reversal of low bone density with a gluten-free diet in children and adolescents with celiac disease.

Osteoporosis is a common finding in adult celiac disease patients; however, there are still few data regarding children and adolescents. In the present study we measured the bone mineral density (BMD) in children and adolescents at diagnosis of celiac disease and after approximately 1 y of a gluten-free diet. BMD was measured at the lumbar spine and in the whole skeleton by dual-energy X-ray absorptiometry in 44 celiac disease patients aged 2.58-20.42 y at diagnosis. BMD was also measured in a subset of 25 patients after 1.4 +/- 0.04 y of a gluten-free diet. BMD was compared with that of 177 healthy control subjects aged 1.52-20.99 y. Lumbar spine and whole-body BMD values at diagnosis of celiac disease were significantly lower than in control subjects (P = 0.015 and P = 0.0001, respectively) after differences in age and anthropomorphic variables were controlled for. The subjects studied after the gluten-free diet had BMD values not significantly different from those of control subjects. In conclusion, children and adolescents with celiac disease have remarkably reduced lumbar spine and whole-body bone density. A gluten-free diet promotes a rapid increase of BMD that leads to a complete recovery of bone mineralization. These results emphasize the need for an early diagnosis and treatment in patients with celiac disease to obtain an adequate peak bone mass at the end of puberty.

Absorptiometry, Photon↗
PubMed2000

Body composition and dietary intakes in adult celiac disease patients consuming a strict gluten-free diet.

BACKGROUND: Celiac disease responds to dietary gluten withdrawal, but data on the long-term effects of gluten-free diets are discordant. OBJECTIVE: Our aim was to evaluate the nutritional status and body composition of adult celiac disease patients consuming a gluten-free diet who were in clinical, biochemical, and histologic remission. DESIGN: We studied 71 patients (51 women and 20 men; mean age: 27 y; range: 17-58 y) and 142 healthy control subjects matched by sex and age. The subjects' height, weight, body mass index, fat and lean mass, and bone mineral content (evaluated by dual-energy X-ray absorptiometry) were measured; a 3-d dietary questionnaire was administered; and total daily energy, fat, carbohydrate, and protein intakes were calculated. RESULTS: The weight, height, and body mass index of male celiac disease patients and the weight and body mass index of female celiac disease patients were significantly lower than the corresponding measurements in control subjects. The fat and lean mass of both male and female patients was significantly different from that of control subjects; however, bone mineral content was significantly lower only in females in whom celiac disease was diagnosed in adulthood. Total energy intake was lower in the patients than in the control subjects (9686 +/- 1569 and 11297 +/- 1318 kJ/d in males and 6736 +/- 1318 and 7740 +/- 1715 kJ/d in females), and the diet of the patients was unbalanced, with a higher percentage of energy as fat and a lower percentage of energy as carbohydrates. CONCLUSIONS: Although strictly compliant with their gluten-free diet and in complete remission, patients with celiac disease showed differences in body composition and dietary intakes compared with control subjects. Strict follow-up and dietary advice in terms of the choice and composition of foods seem necessary to prevent malnutrition.

Absorptiometry, Photon↗
PubMed1996

Reliability of immunologic markers of celiac sprue in the assessment of mucosal recovery after gluten withdrawal.

We studied 47 adults (21 men, 26 women), with biopsy-proven celiac sprue and anti-endomysin antibody (EmA) positivity while untreated, to evaluate the usefulness of both serologic markers of celiac sprue [i.e., immunoglobulin A (IgA)-EmA and total Ig-anti-gliadin (AGA) antibodies] and of a detailed dietary inquiry in predicting the mucosal pattern after gluten withdrawal. A second biopsy was repeated 8-30 months after beginning a gluten-free diet, along with EmA and AGA determinations and the dietary inquiry. Both EmA and AGA were appraised by indirect immunofluorescence on monkey esophagus and rat kidney, respectively. Intestinal biopsy was graded according to Cooke's criteria. After gluten withdrawal, intestinal mucosa reverted to normal in only nine patients. Both EmA and AGA showed high positive but low negative predictive values on intestinal histologic outcome. The positive predictive value of admission of dietary lapses was 100%, whereas the negative predictive value was 39.1%. Neither serologic markers nor dietary inquiries are to be regarded as reliable predictors of intestinal outcome after a gluten-free diet. Biopsy remains the best means of ascertaining mucosal recovery.

Adolescent↗
PubMed1989

Early prediction of relapse during gluten challenge in childhood celiac disease.

Thirty-seven children, in whom celiac disease had been diagnosed because of flat mucosa on a gluten-containing diet and recovery on a gluten-free diet, were challenged with gluten powder, 10 g/day, in addition to an otherwise gluten-free diet. A small intestinal biopsy was performed before the challenge; clinical symptoms, a 1-h blood xylose test, and gliadin antibody measurement were used to establish the timing of the confirmatory biopsy. All but one case relapsed within 205 days (mode, 60 days). In no case was the relapse clinically evident. Raised levels of gliadin antibodies, a fall in xylose absorption, or both predicted the relapse in 37%, 7%, and 57% of cases, respectively. Evaluated individually, each test gave a considerable rate of false negative results. Discriminant coefficients produced for each test were used to compute a score that allowed the classification of patients into relapse/no relapse categories with a good degree of accuracy. The discriminant score rose sharply after only 15 days of challenge, indicating that it is possible to predict the relapse long before any clinical symptom appears.

Antibodies↗
PubMed1990

IgA anti-gliadin antibodies in the monitoring of gluten challenge in celiac disease.

The aim of this study was to evaluate the reliability of serum IgA anti-gliadin antibodies (IgA-AGA) in the monitoring of gluten challenge and in the prediction of mucosal relapse in children with celiac disease (CD) in order to reduce the challenging procedure to a minimum. Serial evaluations of serum IgA-AGA titers and 1-h blood xylose levels were performed in 17 children with celiac disease during gluten challenge. Jejunal biopsy was generally done after two consecutive measurements of positive IgA-AGA. The morphological appearance of the mucosa and intraepithelial lymphocyte infiltration were also evaluated. A serum positive for IgA-AGA was observed in 16 of 17 patients between the 15th and 35th day of challenge. The challenge was concluded in all children after 20-45 days from the introduction of a gluten-containing diet after histological confirmation of CD. Plasma xylose test was less reliable in this respect. We conclude that IgA-AGA measurement by gluten challenge is likely to simplify and allow earlier diagnostic confirmation of celiac disease in children, without intestinal biopsy.

Celiac Disease↗
PubMed1999

Gluten-free diet decreases urinary peptide levels in children with celiac disease.

BACKGROUND: Increased urine secretion of peptides has been found in celiac disease, probably resulting from increased intestinal uptake of peptides caused by damage to the small gut mucosa. METHODS: High-performance liquid chromatography of low-molecular-weight peptides in the urine was performed over 6 months, before and after a gluten-free diet was instituted in children who clinically improved while consuming the diet. RESULTS: A significant decrease of peptide levels was observed in children consuming the gluten-free diet. Certain peptide peaks thought to be gluten related decreased the most after the patients began the diet. CONCLUSIONS: Because the peptides decrease in patients consuming a gluten-free diet, it is reasonable to conclude that such peptides have a mostly dietary origin.

Adolescent↗
PubMed2004

Gluten-free diet has a beneficial effect on chromosome instability in lymphocytes of children with coeliac disease.

OBJECTIVES: Children with coeliac disease (CD) have an increased number of chromosome aberrations in peripheral blood lymphocytes. Whether genetically determined or a secondary phenomenon in CD, chromosome abnormalities may be involved in the predisposition to cancer in CD patients. The aim of the study was to follow a group of children with CD in whom the initial frequency of chromosome aberrations at diagnosis was known and to measure the same variable after a minimum of 2 years on a gluten-free diet. METHODS: Chromosome aberrations in peripheral blood lymphocytes were determined in 17 patients with CD, before and after at least 24 months of a gluten free diet (mean, 33 months), and in 15 healthy children. The differences in the frequency of aberrations were analyzed by Mann-Whitney U test and Wilcoxon matched-pairs signed-ranks test. RESULTS: Twelve patients adhered to the diet and had a significantly lower frequency of chromosome aberrations than did 5 patients not following the diet (0.16% v 1.2%; P = 0.03), whereas at presentation there had been no difference (1.54% v 1.2%; P = 0.09). The frequency of aberrations at follow-up in patients who were diet adherent was significantly lower than at presentation (1.54% v 0.16%; P = 0.02) and remained unchanged in patients who were not diet adherent (1.2% v 1.2%; P = 1). After at least 24 months of a gluten-free diet, children with CD did not differ from healthy control subjects (0.16% v 0.27%; P = 0.54), whereas children not following the diet had an increased frequency of aberrations (1.2% v 0.27%; P = 0.05). CONCLUSIONS: The frequency of chromosome aberrations in peripheral blood lymphocytes of patients with CD decreased significantly on a gluten-free diet. We conclude that genomic instability is a secondary phenomenon, possibly caused by chronic intestinal inflammation.

Adolescent↗
PubMed1999

Gluten-induced nitric oxide and pro-inflammatory cytokine release by cultured coeliac small intestinal biopsies.

OBJECTIVES: To determine whether there was increased nitric oxide (NO) production from coeliac small intestinal biopsies cultured in vitro with gluten and whether the inhibition of NO production could prevent gluten-induced enterotoxicity. The relationship between NO production with the pro-inflammatory cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was evaluated. DESIGN: Small intestinal biopsies from ten patients with treated coeliac disease and six controls were studied. METHODS: Small intestinal biopsies were taken from each patient and set up in culture with Frazer's fraction III (FFIII), a peptic/tryptic digest of gluten, FFIII plus L-NMMA and L-NMMA alone, culture medium alone and ovalbumin which served as a control protein. The biopsies were cultured for 20 h at 37 degrees C. The supernatants were then collected and analysed for nitrite using the Greiss reaction; cytokine levels were determined using ELISA kits. Enterocyte height was determined by microscopy using a calibrated eyepiece graticule and cryostat sections of the cultured biopsies. RESULTS: Coeliac biopsies cultured with FFIII produced significantly greater nitrite compared to culture medium alone (P< 0.05) and this could be blocked with L-NMMA (P< 0.01). A reduction in enterocyte height was seen in coeliac biopsies cultured with FFIII compared to culture medium alone (P < 0.01) and this was ameliorated but not completely blocked when FFIII was cultured with L-NMMA. These changes were not seen in the controls. There was a significant reduction in IL-1beta levels in the supernatant of coeliac biopsies cultured with FFIII compared to culture medium alone (P< 0.05), but when cultured with FFIII and L-NMMA there was a significant increase in IL-1beta levels (P< 0.05). An increase in IFN-gamma levels was also seen when coeliac biopsies were cultured with FFIII and L-NMMA (P< 0.05). This pattern was not seen with TNF-alpha. CONCLUSIONS: Increased levels of NO can be found when coeliac biopsies are cultured with gluten in an in vitro small intestinal culture system, and NO may play a role in the observed enterotoxicity as the inhibition of NO production ameliorates the enterocyte damage. The results suggest that NO is involved in the regulation of pro-inflammatory cytokines, particularly IL-1beta. This is likely to be one of many pathways leading to the observed mucosal pathology in coeliac disease and demonstrates the close interactions between them.

Adolescent↗
PubMed2002

IgA-class transglutaminase antibodies in evaluating the efficacy of gluten-free diet in coeliac disease.

OBJECTIVE: Serum IgA-class tissue transglutaminase antibody has proved effective in screening for coeliac disease. The response to a gluten-free diet has been assessed on the basis of small-intestinal morphology. We investigated whether the tissue transglutaminase antibody test could substitute biopsy in this respect, and whether the test is better than the endomysial antibody test in follow-up. DESIGN: Controlled cross sectional, and follow-up study. METHODS: Serum IgA-class tissue transglutaminase antibodies and endomysial antibodies were determined in 87 coeliac adults on a gluten-free diet. All underwent small bowel biopsy, and the mucosal morphology was interpreted along with Marsh's grading 0-3. In 30 patients histological and serological data could be analysed before and after adopting the diet; Marsh 3 was considered inadequate mucosal recovery during the diet. RESULTS: Of the 87 coeliac patients 27 showed Marsh 3 villous atrophy on gluten-free diet; of these 27, tissue transglutaminase antibody was within normal limits in 16 (59%) and endomysial antibody in 20 (74%). Two (7%) out of 29 with normal mucosa (Marsh 0) had positive tissue transglutaminase antibodies. Six (55%) out of 11 admitting regular dietary lapses remained tissue transglutaminase antibody negative. In the follow-up, serum IgA-class tissue transglutaminase antibody was initially positive in 28 (93%) out of 30 untreated patients; even a significant decrease in tissue transglutaminase antibody did not guarantee mucosal recovery. CONCLUSIONS: A substantial number of coeliac patients with negative tissue transglutaminase or endomysial antibodies may still have manifest mucosal villous atrophy. Small bowel biopsy is therefore still necessary to ensure that the gluten-free diet is adequate.

Biopsy↗
PubMed2005

Report of a collaborative trial to investigate the performance of the R5 enzyme linked immunoassay to determine gliadin in gluten-free food.

OBJECTIVE: Analytical methods for measurements of gluten in the low level range of 20-200 ppm of gluten, as required for gluten-free food, have never been endorsed by the Codex Alimentarius. With the aim of investigating standardized and reliable methods for the detection of gliadin in food with detection limits lower than 200 ppm, as proposed by the Codex Alimentarius, the Working Group on Prolamin Analysis and Toxicity (WGPAT) coordinated a large collaborative study to validate a monoclonal antibody based ELISA, which uses an antibody (R5) against rye secalins. METHODS: Twelve food samples in which gliadin was present in the range of 0-168 ppm were analysed with two different commercially available R5 ELISA tests and a special extraction solvent, based on a reducing and a dissociating agent designed to extract heat denatured proteins. Twenty laboratories participated in this study. RESULTS: Recovery values ranged from 65 to 110% in general. The repeatability (RSDr) and reproducibility (RSDR) figures ranged between 13 and 25, resp. 23 and 47 for one test, and between 11 and 22, resp. 25 and 33 for the other. CONCLUSION: Both assays are comparable and robust. The repeatability and reproducibility data are in a range that is acceptable for ELISAs. Kits from both suppliers fulfilled performance criteria of regular ELISA methods, and it is shown that both ELISA kits guarantee a sensitivity of 1.5 ppm gliadin for gluten-free food.

Antibodies, Monoclonal↗
PubMed2004

Gynecologic and obstetric findings related to nutritional status and adherence to a gluten-free diet in Brazilian patients with celiac disease.

This study shows a broad analysis of gynaecological and obstetrical disturbances in patients with celiac disease in relation to their nutritional status and adherence to a gluten-free diet. Seventy-six adult celiac patients were analyzed according to nutritional status and 18 children/adolescents to gluten-free diet adherence. As controls, 84 adults and 22 adolescents with irritable bowel syndrome were used The significant findings were observed as follow: adult celiac patients, irrespective of the nutritional status, were younger than controls, presented delayed menarche, secondary amenorrhea, a higher percentage of spontaneous abortions, anemia and hypoalbuminemia. No differences were observed regarding the number of pregnancies, age at menopause and duration of the reproductive period. After treatment, patients presented with normal pregnancies and one patient presented spontaneous abortion. The adolescents who were not adherent to gluten-free diet presented delayed menarche and secondary amenorrhea. In conclusion, gluten per se could explain the disturbances and malnutrition would worsen the disease in a consequent vicious cycle. Therefore, celiac disease should be included in the screening of reproductive disorders.

Abortion, Spontaneous↗
PubMed2002

The structure and properties of gluten: an elastic protein from wheat grain.

The wheat gluten proteins correspond to the major storage proteins that are deposited in the starchy endosperm cells of the developing grain. These form a continuous proteinaceous matrix in the cells of the mature dry grain and are brought together to form a continuous viscoelastic network when flour is mixed with water to form dough. These viscoelastic properties underpin the utilization of wheat to give bread and other processed foods. One group of gluten proteins, the HMM subunits of glutenin, is particularly important in conferring high levels of elasticity (i.e. dough strength). These proteins are present in HMM polymers that are stabilized by disulphide bonds and are considered to form the 'elastic backbone' of gluten. However, the glutamine-rich repetitive sequences that comprise the central parts of the HMM subunits also form extensive arrays of interchain hydrogen bonds that may contribute to the elastic properties via a 'loop and train' mechanism. Genetic engineering can be used to manipulate the amount and composition of the HMM subunits, leading to either increased dough strength or to more drastic changes in gluten structure and properties.

Amino Acid Sequence↗