Malignancy and mortality in a population-based cohort of patients with coeliac disease or 'gluten sensitivity'

Aim: To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland.

Methods: A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated.

Results: A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin anti-bodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin's lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population.

Conclusion: Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity. © 2007 The WJG Press. All rights reserved.

Fermentation of heated gluten systems by gut microflora

The Maillard reaction causes changes to protein structure and occurs in foods mainly during thermal treatment. Melanoidins, the final products of the Maillard reaction, may enter the gastrointestinal tract, which is populated by different species of bacteria. In this study, melanoidins were prepared from gluten and glucose. Their effect on the growth of faecal bacteria was determined in culture with genotype and phenotype probes to identify the different species involved. Analysis of peptic and tryptic digests showed that low molecular mass products are formed from the degradation of melanoidins. Results showed a change in the growth of bacteria. This in vitro study demonstrated that melanoidins, prepared from gluten and glucose, affect the growth of the gut microflora.

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

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.

Gliadin antibody detection in gluten enteropathy

Circulating antigliadin antibody has been described in patients with gluten enteropathy although the prevalence varies in different studies. It has been suggested that the investigation for antigliadin antibody might be useful as a screening test. The object of the present study was to evaluate two different techniques for assaying these antibodies - an indirect immunofluorescent method and an enzyme-linked immunosorbent assay (ELISA). Antibodies were assayed in the sera of 102 patients in whom jejunal biopsies were also obtained. The specificity of both tests was greater than 95%, and the correlation between the presence of antibody and histology was significant (p <0.005), though the sensitivity of each test was less than 70%.

Developing Food Products For Consumers on a Gluten Free Diet

There is a significant increase in people that choose to follow an avoidance diet, especially excluding gluten. Unlike previously, there is now a demand for ‘no compromise’ gluten-free cereal products that have the same properties as their wheat contain counterparts. This is very challenging for the bakers and the cereal technologists due to the functional role of the gluten network in some of these products. Numerous combinations of raw materials form natural sources have been studied and critically evaluated in this review. Most of the gluten-free products are made of native and modified starches blended with different hydrocolloids due to their structure-building and water binding properties. These ingredients are added to a gluten-free flour, such as rice and corn. The legislation framework, formulations for manufacturing of highl nutritional value bread, pasta and cakes/biscuits as well as quality assurance aspects for the gluten-free manufacturers are discussed in this review.

Intra-epithelial T cells in coeliac disease

Coeliac disease is an enteropathy associated with dietary gluten which occurs in individuals with a genetic predisposition. The pathogenesis remains obscure although it is clear that only certain parts of the gliadin molecule are toxic and there is considerable evidence of immunological activity, including antibody production. In this issue of European Journal of Gastroenterology and Hepatology Carton et al. present evidence in favour of an inherent depletion of CD4CD8 T cells, which could result in a loss of oral tolerance to ingested gliadin. Using flow cytometry they also demonstrated that the classic T-cell infiltration of coeliac disease is not due to an increase in T cells but is an apparent increase associated with a relative decrease in enterocytes as a result of the change in architecture of the mucosa. These could be important fundamental observations in helping to unravel the pathogenesis of coeliac disease.

Coeliac disease detected by screening is not silent--simply unrecognized

Coeliac disease (CD) is associated with a wide spectrum of clinical presentation and may be overlooked as a diagnosis. There is some evidence that untreated CD is associated with a doubling of mortality, largely due to an increase in the incidence of malignancy and small intestinal lymphoma, which is decreased by a strict gluten-free diet. We studied the clinical features of screening-detected coeliacs compared to age- and sex-matched controls as a 3-year follow-up to a population screening survey, and followed-up subjects who had had CD-associated serology 11 years previously to determine whether they have CD or an increased mortality rate compared to the general population. Samples of the general population (MONICA 1991 and 1983) were screened for CD-associated serology and followed-up after 3 and 11 years, respectively, and assessed by a clinical questionnaire, screening blood tests and jejunal biopsy. Mortality rates for 'all deaths' and 'cancer deaths' were compared in subjects with positive serology in 1983 with reference to the general population. Thirteen coeliacs were diagnosed by villous atrophy following screening, compared to two patients with clinically detected CD, giving a prevalence of 1:122. Clinical features or laboratory parameters were not indicative of CD compared to controls. Subjects with positive serology followed up after 11 years did not have an excess mortality for either cancer deaths or all causes of death. Screening-detected CD is rarely silent and may be associated with significant symptoms and morbidity. In this limited study with small numbers, there does not appear to be an increased mortality from screening-detected CD, although the follow-up may be too short to detect any difference.

Factors associated with serum antibodies to reticulin, endomysium, and gliadin in an adult population

Gluten sensitivity is thought to be significantly under-diagnosed in the population.

Liver abnormalities associated with celiac sprue. How common are they, what is their significance, and what do we do about them?

We prospectively measured serum alkaline phosphatase (ALP), aspartate and alanine transaminase (AST/ALT), and tested sera for antinuclear, smooth-muscle, and antimitochondrial antibodies (ANA, SMA, AMA) in our patients with celiac sprue to determine the prevalence of associated liver abnormalities and its relevance to clinical management. Of 129 patients, ALP was the only elevated enzyme in 12 (9%) and in most cases was not thought to reflect significant liver disease. Seventeen (13%) had elevated AST and/or ALT with normal ALP. Levels normalized in 15 patients after dietary gluten exclusion and remained elevated in 2 noncompliers. Two patients (2%) with elevated AST, ALT, and ALP underwent further investigation: one had negative autoantibodies, liver biopsy, and endoscopic retrograde cholangiography and the other had ANA-positive chronic active hepatitis; enzymes in both cases improved with a gluten-free diet. There was no significant association between elevated AST/ALT and positive ANA/SMA; no patient had AMA. Abnormalities in liver enzymes are common in celiac sprue, but usually respond to dietary gluten exclusion. We propose that there is no need for invasive liver investigation in these patients unless there is more specific evidence of primary liver disease or failure of dietary response.

Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.

Investigation of molecular markers in the diagnosis of refractory coeliac disease in a large patient cohort

Some patients with coeliac disease, despite strict adherence to a gluten-free diet, continue to have significant symptoms and/or a severe small intestinal histological lesion. The term "refractory coeliac disease" (rCD) is used to describe this condition. The purpose of this study was to investigate the value of tissue molecular markers reported to help in the diagnosis of rCD.

Essential and toxic elements in infant foods from Spain, UK, China and USA

Spanish gluten-free rice, cereals with gluten, and pureed baby foods were analysed for essential macro-elements (Ca and Na), essential trace elements (Fe, Cu, Zn, Mn, Se, Cr, Co and Ni) and non-essential trace elements (As, Pb, Cd and Hg) using ICP-MS and AAS. Baby cereals were an excellent source of most of the essential elements (Ca, Fe, Cu, Mn and Zn). Sodium content was high in pureed foods to improve their flavour; fish products were also rich in Se. USA pure baby rice samples had the highest contents of all studied essential elements, showing a different nutrient pattern compared to those of other countries. Mineral fortification was not always properly stated in the labelling of infant foods. Complementary infant foods may also contain significant amounts of contaminants. The contents of Hg and Cd were low enough to guarantee the safety of these infant foods. However, it will be necessary to identify the source and reduce the levels of Pb, Cr and As in Spanish foods. Pure baby rice samples contained too much: Pb in Spain; As in UK; As, Cr and Ni in USA; and Cr and Cd in China.

Inorganic arsenic contents in rice-based infant foods from Spain, UK, China and USA

Spanish gluten-free rice, cereals with gluten, and pureed baby foods were analysed for total (t-As) and inorganic As (i-As) using ICP-MS and HPLC-ICP-MS, respectively. Besides, pure infant rice from China, USA, UK and Spain were also analysed. The i-As contents were significantly higher in gluten-free rice than in cereals mixtures with gluten, placing infants with celiac disease at high risk. All rice-based products displayed a high i-As content, with values being above 60% of the t-As content and the remainder being dimethylarsinic acid (DMA). Approximately 77% of the pure infant rice samples showed contents below 150 µg kg(-1) (Chinese limit). When daily intake of i-As by infants (4-12 months) was estimated and expressed on a bodyweight basis (µg d(-1) kg(-1)), it was higher in all infants aged 8-12 months than drinking water maximum exposures predicted for adults (assuming 1 L consumption per day for a 10 µg L(-1) standard).

Survey of arsenic and its speciation in rice products such as breakfast cereals, rice crackers and Japanese rice condiments

Rice has been demonstrated to be one of the major contributors to arsenic (As) in human diets in addition to drinking water, but little is known about rice products as an additional source of As exposure. Rice products were analyzed for total As and a subset of samples were measured for arsenic speciation using high performance liquid chromatography interfaced with inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). A wide range of rice products had total and inorganic arsenic levels that typified those found in rice grain including, crisped rice, puffed rice, rice crackers, rice noodles and a range of Japanese rice condiments as well as rice products targeted at the macrobiotic, vegan, lactose intolerant and gluten intolerance food market. Most As in rice products are inorganic As (75.2-90.1%). This study provides a wider appreciation of how inorganic arsenic derived from rice products enters the human diet. (C) 2008 Elsevier Ltd. All rights reserved.