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Effect of gender on the manifestations of celiac disease: evidence for greater malabsorption in men.

OBJECTIVE: Because celiac disease is a female-predominant disease we investigated the influence of gender on clinical manifestations of the disease in the United States. MATERIAL AND METHODS: Data were obtained on biopsy-proven adult patients with celiac disease from a database of patients seen between 1981 and 2001 in a University-based referral center. Z scores were calculated to adjust for age, ethnicity and gender using the National Health and Nutrition Examination Survey database as controls. RESULTS: The cohort consisted of 323 patients (211 F, 112 M). Men had a shorter duration of symptoms than women (p=0.006). There was no gender difference in the age at diagnosis or mode of presentation. Body mass index (BMI), mean hemoglobin and ferritin values were lower in women than in men, but the Z scores for these values were not significantly different, indicating that the differences are physiological. All lipid values were low (negative Z scores). Men had lower total cholesterol (162.0+/-46.5mg/dl) compared to women (181.0+/-40.0mg/dl), p=0.02 and lower Z scores (-1.10+/-1.1) compared to women (-0.71+/-0.9), p=0.04. Men had lower bone density T scores at the radius (p=0.07). Autoimmune diseases were present in 30.7% with a female to male ratio of 1:1, compared to the general population in which 3.2% have autoimmune diseases with a female predominance. CONCLUSIONS: Most gender differences in celiac disease are physiological. However, men have indirect evidence of greater malabsorption than females and have female-predominant associated diseases when they present with celiac disease.

Adult↗

Serum nitric oxide levels in children with celiac disease.

OBJECTIVES: To determine serum nitric oxide levels in pediatric patients with celiac disease and to compare them with the results obtained after 1 year of gluten-free diet. METHODS: We studied serum nitric oxide levels in 41 newly diagnosed patients with celiac disease. Serum levels of nitric oxide were reevaluated after 1 year of gluten-free diet in 23 of them. Mean age was 10.4 +/- 3.4 years (range 2-17 years). RESULTS: The levels of nitric oxide in pretreatment 41 patients with celiac disease and healthy children were detected as 198.33 +/- 20.22 micromol/L and 135.63 +/- 21.17 micromol/L, respectively (P = 0.0001). Serum nitric oxide level, measured in the blood samples 1 year after gluten-free diet, was 148.27 +/- 27.25 micromol/L (P = 0.001). Serum nitric oxide levels were statistically correlated with the degree of histologic changes in celiac disease. In the patients with celiac disease, pretreatment level of nitric oxide was not correlated with the levels of triglyceride, cholesterol, albumin, aspartate aminotransferase, alanine aminotransferase, or creatine kinase. We found correlations with the level of nitric oxide and Hb, mean corpuscular volume, and ferritin. CONCLUSION: Higher serum nitric oxide levels found in children who had not compliance with gluten-free diet suggested the role of serum nitric oxide as an indicator of diet compliance. Because determination of serum nitric oxide is a simple, rapid, cheap, noninvasive, and highly sensitive method for celiac disease, we think that this parameter can be used in the evaluation of diet compliance in children with celiac disease or even instead of gluten challenge, due to more noninvasive property.

Adolescent↗

Purification of fibroblast-derived celiac disease autoantigen molecules.

We have recently purified autoantigen polypeptides reacting with celiac disease patient sera IgA from the extracellular noncollagenous matrix compartment of fetal lung tissue. These molecules trigger the production of different tissue antibodies, the so-called antireticulin and antiendomysium antibodies in celiac disease. In the present report, we show that fibroblasts synthesize and secrete celiac disease autoantigen molecules. The secretion product, reactive with IgA from celiac disease patients, is a large-molecular-weight protein aggregate. When the protein complex was treated with 4 M guanidinium hydrochloride and 0.1% SDS, 11 monocomponent polypeptides could be detected by PAGE. Of these, four single polypeptides with molecular weights of 17,000-39,500 and isoelectric points of 5.0-7.0 were observed to react with IgA separated from sera of children with celiac disease. The polypeptide molecules produced by fibroblasts in vitro bound to antireticulin and antiendomysium antibodies but not to antigliadin antibodies. The present observations show that tissue antibodies found to be specifically associated with celiac disease are generated against a synthesis product of fibroblasts, a cell-type known to synthesize a number of biologically active polypeptides. The fibroblast-derived extracellular matrix proteins and the formed autoantibodies may be important in the pathogenesis of gluten-sensitive enteropathy.

Antibodies↗

Prevalence of Celiac disease among children in Finland.

BACKGROUND: Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that positive findings correlate with specific HLA haplotypes. METHODS: Serum samples were collected from 3654 students (age range, 7 to 16 years) in 1994 and screened in 2001 for endomysial and tissue transglutaminase antibodies. HLA typing was also performed on stored blood samples. All antibody-positive subjects were asked to undergo small-bowel biopsy in 2001. RESULTS: Of the 3654 subjects, 56 (1.5 percent) had positive antibody tests, as determined in 2001. Results of the two antibody tests were highly concordant. As of 1994, none of the subjects had received a clinical diagnosis of celiac disease, but 10 who had positive tests for both antibodies in serum obtained in 1994 received the diagnosis between 1994 and 2001. Of the 36 other subjects with positive antibody assays who agreed to undergo biopsy in 2001, 27 had evidence of celiac disease on biopsy. Thus, the estimated biopsy-proved prevalence was 1 case in 99 children. All but two of the antibody-positive subjects had either the HLA-DQ2 or the HLA-DQ8 haplotype. The prevalence of the combination of antibody positivity and an HLA haplotype associated with celiac disease was 1 in 67. CONCLUSIONS: The presence of serum tissue transglutaminase and endomysial autoantibodies is predictive of small-bowel abnormalities indicative of celiac disease. There is a good correlation between autoantibody positivity and specific HLA haplotypes. We estimate that the prevalence of celiac disease among Finnish schoolchildren is at least 1 case in 99 children.

Adolescent↗

Are complicated forms of celiac disease cryptic T-cell lymphomas?

We assessed the clonality of duodenal mucosal T cells in patients with celiac disease and controls. Fifteen adult patients were studied. Four patients had a complicated celiac disease, 3 did not respond to a gluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had an untreated celiac disease responsive to a gluten-free diet. Histological examination of duodenal biopsies of these 11 patients showed benign-appearing celiac disease without evidence of lymphoma. Four patients with nonulcer dyspepsia and normal duodenal biopsies served as controls. TCRgamma gene rearrangements were analyzed by multiplex polymerase chain reaction on DNA extracted from duodenal biopsies. Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmed by DNA sequencing of the junctional region in 3 cases and by hybridization with clone-specific oligoprobes. Patients with celiac disease responsive to gluten-free diet had mainly a polyclonal pattern, with 1 of them having an oligoclonal rearrangement. An oligoclonal pattern was also observed in 2 control patients. Three patients with complicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found in the enteropathic duodenojejunum and peripheral blood in the patient with large-cell lymphoma with bone marrow invasion. This study suggests that complicated celiac disease is a cryptic T-cell lymphoma.

Adult↗

[First determination of the prevalence of celiac disease in a Portuguese population].

UNLABELLED: The prevalence of celiac disease is unknown in Portugal. In European countries the prevalence is between 1:200 and 1:400. The incidence obtained through diagnosed cases in the paediatric gastroenterology units in Portugal was 1:3648. To determine the best current celiac disease screening method and its prevalence in a portuguese population, 536 sera of teenagers with 14 years +/- 6 months from Braga town schools were tested as follows: a) total IgA, b) anti-tissue transglutaminase antibodies c) anti-endomysium antibodies (AEA). One female adolescent, with negative AEA and anti-transglutaminase antibodies had a diagnosed celiac disease; this patient was under appropriate diet. Eleven adolescents had positive anti-transglutaminase antibodies and 4 of these had also positive AEA. A jejunal biopsy was carried out on the latter adolescents. Three presented intestinal villous atrophy, 2 a flat mucosa and 1 a moderate atrophy. One female adolescent had a normal mucosa. The prevalence was 1:134, [confidence interval at 95%, 1:53-1:500]. CONCLUSIONS: Presently, total IgA with determination of anti-tissue transglutaminase antibodies is apparently the best screening method; it is less expensive test and, given the use of ELISA, less dependent on the observer. The celiac disease prevalence found in the present study falls within the range of prevalence recently found in other European populations, which implies that the celiac disease is under-diagnosed in Portugal.

Adolescent↗

Calcaneal ultrasound attenuation and vitamin-D-receptor genotypes in celiac disease.

BACKGROUND: Osteopenia is common in patients with celiac disease and is believed to result from malnutrition. Osteoporosis in otherwise healthy individuals is related to genetically determined polymorphisms within the vitamin-D-receptor (VDR) gene. We hypothesized that in celiac patients particular genes of the VDR enhance the susceptibility for malnutrition-associated low-bone density. METHODS: We determined allelic frequencies within the VDR gene by restriction fragment length polymorphism analysis in 92 patients with celiac disease (age, 15-83 years). Thirty-eight patients were on a gluten-free diet; 54 patients did not adhere to a diet. The determined VDR polymorphisms in 111 unrelated newborns served as controls. Osteopenia was determined by means of ultrasound measurements of the calcaneus (n = 78). Bone turnover was estimated by osteocalcin determination (n = 60). RESULTS: There was no difference in the frequency of the VDR gene polymorphisms in patients with celiac disease compared with controls. Adjusted ultrasound measures of the calcaneus were low in 47% of patients, but there was no difference of the VDR gene frequencies in these patients compared with those with normal ultrasound results or controls. Bone turnover was higher in patients without a gluten-free diet (P = 0.02). Again, there was no association with any particular VDR gene. CONCLUSIONS: Patients with celiac disease frequently have osteopenia, which is not related to any of the determined genes within the VDR.

Adolescent↗

Analyzing the peripheral blood antibody repertoire of a celiac disease patient using phage antibody libraries.

Celiac disease (CD) is an autoimmune enteropathy characterized by intestinal malabsorption and immunological responses to dietary gliadins and an auto antigen located in the endomysium. The latter has recently been identified as the enzyme tissue transglutaminase (tTG). The linkage between gliadins, tTG and the autoimmune response has still to be clarified. In this work we report the production and analysis of a phage antibody library from the peripheral blood lymphocytes (PLB) of a CD patient. The library contained polyreactive and monoreactive antibodies to alpha-gliadin, to the dietary antigen beta-lactoglobulin, but not to tTG. The majority of the VH regions of the anti-alpha-gliadin antibodies belonged to the VH 4 family. The possibility of exploiting phage display antibodies as tools to study the molecular events associated with CD is discussed.

Adult↗

[Celiac disease, laboratory updates].

A celiac disease update review and a case report are presented, especially concerning a Clinical Pathology Laboratory approach. Implemented basic research, case finding strategy and information technologies are the key tools for a better understanding of the multi-etiological features of this disease. By these tools it will be achieved appropriateness in diagnosing and monitoring of the related clinical pictures.

Adult↗

Changes in body composition, substrate oxidation, and resting metabolic rate in adult celiac disease patients after a 1-y gluten-free diet treatment.

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.

Adolescent↗

Mortality in celiac disease.

The mortality experienced by a cohort of 653 patients with celiac disease in Edinburgh and the Lothian region has been analyzed. Mortality overall was 1.9-fold (95% confidence limits, 1.5-2.2) that of the general population (115 deaths observed, 61.8 expected; p less than 0.0001). The increased mortality was greatest within 1 yr of diagnosis of celiac disease and steadily declined over time with the excess mortality being concentrated at ages 45-54 yr in men and 55-64 yr in women. Celiac disease was mentioned on the death certificate in 33 cases but in only 10 was it given as the underlying cause of death. Of 17 deaths from lymphoproliferative diseases (0.55 expected, p less than 0.001), 8 occurred within 2 yr of diagnosis of celiac disease compared with 8 (0.37 expected, p less than 0.001) occurring greater than 5 yr after diagnosis. Esophageal cancer was certified as the cause of four deaths (0.47 expected, p less than 0.01). In men mortality from all other malignant disease was also increased (15 deaths observed; 6.4 expected, p less than 0.01), but most of these deaths occurred within 5 yr of the diagnosis of celiac disease. In contrast, there was no deficit in deaths from ischemic heart disease or stroke and the mortality rate in those diagnosed in childhood as having celiac disease was similar to the general population.

Age Factors↗

Screening for celiac disease: a prospective study on the value of noninvasive tests.

OBJECTIVE: Celiac disease is frequently diagnosed in patients with nonspecific abdominal symptoms. Therefore, highly sensitive, specific, and simple noninvasive screening tests are needed. METHODS: This study compared the usefulness of IgG- and IgA-antigliadin antibodies, IgA-endomysial antibodies, and intestinal permeability in diagnosing celiac disease in 102 adult patients with nonspecific abdominal symptoms. In addition, all patients underwent small bowel biopsy as a gold standard for the diagnosis of celiac disease. RESULTS: Forty-nine patients were ultimately diagnosed as having celiac disease because of flat mucosa. Flatulence and signs and symptoms dating back to childhood were more frequent and abdominal pain less frequent (p < 0.05) in celiac disease but were not helpful for screening. IgA-endomysial antibodies showed a sensitivity and specificity of 100%; an altered intestinal permeability had also a 100% sensitivity, but only 55% specificity. IgG- and IgA-antigliadin antibodies' sensitivity (73% and 82%, respectively) and specificity (74% and 83%, respectively) were much lower. Combining the two antigliadin antibodies did not significantly improve the sensitivity and specificity. CONCLUSIONS: Our data show the advantage of IgA-endomysial antibodies for screening of celiac disease except in the case of patients with IgA-deficiency or dermatitis herpetiformis. In these patients, the permeability test could improve noninvasive differential diagnosis.

Adult↗

Natural variation in toxicity of wheat: potential for selection of nontoxic varieties for celiac disease patients.

BACKGROUND & AIMS: Celiac disease (CD) is an intestinal disorder caused by T-cell responses to peptides derived from the gluten proteins present in wheat. Such peptides have been found both in the gliadin and glutenin proteins in gluten. The only cure for CD is a lifelong gluten-free diet. It is unknown, however, if all wheat varieties are equally harmful for patients. We investigated whether wheat varieties exist with a natural low number of T-cell-stimulatory epitopes. METHODS: Gluten proteins present in public databases were analyzed for the presence of T-cell-stimulatory sequences. In addition, wheat accessions from diploid (AA, SS/BB, and DD genomes), tetraploid (AABB), and hexaploid (AABBDD) Triticum species were tested for the presence of T-cell-stimulatory epitopes in gliadins and glutenins by both T-cell and monoclonal antibody-based assays. RESULTS: The database analysis readily identified gluten proteins that lack 1 or more of the known T-cell-stimulatory sequences. Moreover, both the T-cell- and antibody-based assays showed that a large variation exists in the amount of T-cell-stimulatory peptides present in the wheat accessions. CONCLUSIONS: Sufficient genetic variation is present to endeavor the selection of wheat accessions that contain low amounts of T-cell-stimulatory sequences. Such materials may be used to select and breed wheat varieties suitable for consumption by CD patients, contributing to a well-balanced diet and an increase in their quality of life. Such varieties also may be useful for disease prevention in individuals at risk.

Celiac Disease↗

[Celiac disease with occipital calcifications: 2 late cases].

The association of celiac disease, epilepsy and occipital calcifications with initial clinical manifestations of epilepsy during the first two decades of life with an often progressive and variable course and clinical expression of malabsorption has recently been described. Two cases of celiac disease with occipital calcifications and a presentation with neurologic symptoms in adulthood are reported. The first case is that of a 40-year-old male who presented recurrent and alternating pure brachial monoparesis and later acute abdominal pain following which celiac sprue was diagnosed. The second case is that of a 53-year-old woman diagnosed with celiac sprue 20 years before, presenting permanent myoclonus in the lower limbs which were progressive in severity, ataxic march and generalized tonoclonic seizures. Both patients had bilateral occipital calcifications on CT and celiac disease was demonstrated on biopsy. The first case also showed marked signal alteration in the white matter on MRI. Celiac disease with cerebral calcifications presents also in adulthood with atypical clinical manifestations. Suspicion of celiac disease may be confirmed by non-invasive methods such as antigliadin and antiendomysium antibody determination. CT imaging is characteristic.

Adult↗

Osteoporosis in a north american adult population with celiac disease.

OBJECTIVE: Osteoporosis, common in European and South American adults with celiac disease, has not been reported in those patients with celiac disease residing in North America. We therefore evaluated bone density in a group of patients from the United States. METHODS: Patients (105 women and 23 men) with celiac disease, who had completed a questionnaire and had bone mineral density (BMD) measured by dual energy x-ray absorptiometry, were evaluated. The patients were an average age of 56 yr old (range 21-83 yr) and had been on a gluten-free diet from 0 months to 46 yr (mean 7.5 yr). RESULTS: Osteoporosis (T score < -2.5) was present in 34% of the patients at the lumbar spine, 27% at the femoral neck, and 36% at the radius. Low bone mass (T score between -1.0 and -2.5) was present in 38% at the lumbar spine, 44% at the femoral neck, and 32% at the radius. When compared to age-matched controls, men were more severely affected than women. BMD did not differ between those on a gluten-free diet and those who had not begun therapy. BMD was remeasured 16 +/- 2 months after beginning a gluten-free diet in 5 patients; it increased by 7.5% at the femoral neck (p < 0.02). In 16 patients who had followed a gluten-free diet for an average of 12 yr, BMD remained stable over an additional 2 yr of observation. CONCLUSIONS: Osteoporosis and low bone mass often affect North American adults with celiac disease, whether or not they are on dietary therapy. Routine screening for osteoporosis is indicated in patients with celiac disease.

Absorptiometry, Photon↗

Endoscopy in celiac disease.

PURPOSE OF REVIEW: The primary objective of this review is to highlight the evidence for the role of endoscopy in celiac disease. RECENT FINDINGS: Evidence is presented that the endoscopic markers of celiac disease are specific although not sensitive for the disease. Villous atrophy, the hallmark of celiac disease, is patchy in the duodenum, and various techniques may identify areas of villous atrophy. These methods include magnification endoscopy and chromoendoscopy. The most recent innovation, video capsule endoscopy, may be of value in the diagnosis of celiac disease and in the assessment of patients with complicated celiac disease. SUMMARY: Endoscopy and duodenal biopsies are the mainstay for diagnosing celiac disease. Although characteristic endoscopic features may be useful, their absence does not exclude celiac disease. Random biopsy, even of normal-appearing mucosa is necessary for the diagnosis of celiac disease.

Celiac Disease↗