Making oats safer for patients with coeliac disease

(Table is included in full-text article). Studies suggest that oats can be tolerated in the gluten-free diet by a majority of patients with coeliac disease. Concerns remain, however, about the possibility of contamination of commercially available oat products by wheat, barley and rye. The R5 ELISA allows the identification and quantification of wheat, barley and rye prolamins, and has demonstrated significant contamination in a range of products. If patients with coeliac disease are to take oats, it is important that those consumed are free of contamination. This assay should allow the identification of safe oat products.     

In vivo gluten ingestion in coeliac disease

Studies to determine the nature of the cereal component toxic to patients with coeliac disease have concentrated on wheat due to its nutritional importance. A number of in vitro studies have indicated the presence of one or more coeliac-disease-activating epitopes with the N terminus of the A gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acid 31-49 of A gliadin. Changes induced by this peptide included a decrease in the ratio of villous height to crypt depth, a decrease in enterocyte surface cell height and an increase in intra-epithelial lymphocyte count. There was evidence of mRNA for the pro-inflammatory cytokincs interferon gamma and interleukin 2 within 2 h of the in vivo challenge. We examined electron-microscopically biopsies from patients with coeliac disease challenged with gluten to determine the subcellular sites where gliadin co-localised with T-cell receptor subunits and HLA antigens. There were differences in co-localisation patterns between treated and untreated coeliac patients. These differences and the different patterns of gliadin staining within enterocytes of coeliac patients and controls, observed by others, suggest that gliadin may be metabolised via a different immunogenic pathway in coeliac disease. This might result in an abnormal presentation to the immune system, triggering a pathogenic, rather than a tolerogenic response.     

Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease

OBJECTIVE: Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats. MATERIAL AND METHODS: The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months. RESULTS: All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized. CONCLUSIONS: Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.     

Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease

Objective. Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats. Material and methods. The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months. Results. All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized. Conclusions. Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.     

Lack of cellular and humoral immunological responses to oats in adults with coeliac disease

OBJECTIVE: Recent research suggests that oats do not harm intestinal villi in adults with coeliac disease. As the immunological effects of oats have not been examined in detail, it was decided to compare the immunological responses of a gluten free diet including oats with those of a conventional gluten free diet. DESIGN: A randomised controlled intervention study over 6-12 months. SUBJECTS: Forty adults with newly diagnosed coeliac disease and 52 with coeliac disease in remission were examined. INTERVENTION: The effects of a gluten free diet including oats and a conventional gluten free diet were compared. MAIN OUTCOME MEASURES: Serum levels of gliadin and reticulin antibodies as well as numbers of intraepithelial lymphocytes (IELs) in intestinal mucosa were examined before and after the intervention. RESULTS: The rate of disappearance of gliadin and reticulin antibodies did not differ between the diet groups in patients with newly diagnosed coeliac disease. Oats also had no effect on gliadin or reticulin antibody levels in the patients with remission. The number of IELs decreased similarly regardless of the diet of newly diagnosed patients, and no increase in the number of IELs was found in the patients in remission with or without oats. CONCLUSIONS: These results strengthen the view that adult patients with coeliac disease can consume moderate amounts of oats without adverse immunological effects.     

Avenins from different cultivars of oats elicit response by coeliac peripheral lymphocytes

OBJECTIVE: The avoidance of oats in coeliac patients is still controversial. If oats is confirmed to be safe, it would be a valuable component and offer more variation in a gluten-free diet. The aim of this work was to evaluate whether avenins from different varieties of oats show different abilities in the activation of coeliac peripheral lymphocytes. MATERIAL AND METHODS: In order to assess whether the immunogenic effect of oats varies according to the cultivar, peripheral lymphocytes from 10 coeliac children were exposed to avenins from four different oats varieties: Lampton, Astra, Ava and Nave. Lymphocyte proliferation and interferon-gamma (IFN-gamma) release in the culture medium were measured as indexes of immune activation. RESULTS: All the varieties of oats tested were immunogenic, with Lampton and Ava avenins inducing lymphocyte activation similar to that activated by wheat gliadin, while Astra and Nave avenins showed less immunogenicity, but still with a measurable effect. CONCLUSIONS: There are still concerns about the suitability of including oats in a gluten-free diet. Coeliac patients consuming oats-containing food should be carefully monitored, until there is more evidence to show the safety of oats and varieties of low-toxicity oats.     

Avenins from different cultivars of oats elicit response by coeliac peripheral lymphocytes

Objective. The avoidance of oats in coeliac patients is still controversial. If oats is confirmed to be safe, it would be a valuable component and offer more variation in a gluten-free diet. The aim of this work was to evaluate whether avenins from different varieties of oats show different abilities in the activation of coeliac peripheral lymphocytes. Material and methods. In order to assess whether the immunogenic effect of oats varies according to the cultivar, peripheral lymphocytes from 10 coeliac children were exposed to avenins from four different oats varieties: Lampton, Astra, Ava and Nave. Lymphocyte proliferation and interferon-gamma (IFN-γ) release in the culture medium were measured as indexes of immune activation. Results. All the varieties of oats tested were immunogenic, with Lampton and Ava avenins inducing lymphocyte activation similar to that activated by wheat gliadin, while Astra and Nave avenins showed less immunogenicity, but still with a measurable effect. Conclusions. There are still concerns about the suitability of including oats in a gluten-free diet. Coeliac patients consuming oats-containing food should be carefully monitored, until there is more evidence to show the safety of oats and varieties of low-toxicity oats.     

Unkilned and large amounts of oats in the coeliac disease diet: A randomized,controlled study

Objective. There is evidence for the long-term safety of oats as part of a gluten-free diet in coeliac disease (CD). Oats is generally processed by kilning, which theoretically may change its antigenic properties and be the reason that it is tolerated by patients with CD. The aim of this study was to investigate the suitability of large amounts of unkilned oats, comparing its use with kilned oats in adult coeliac patients. Material and methods. The study group included 13 men and 19 women with CD in remission. The goal of daily intake of oats was 100 g during one year. These patients using oats as part of their gluten-free diet were randomized to two treatment groups. One group used regular oats and the other unkilned oats. After 6 months the patients changed the treatment groups. Food intake, symptoms, histology of the small intestine and the levels of endomysial antibodies were noted. Results. No marked changes were found in the duodenal biopsies, in the levels of endomysial antibodies or in the well-being of the patients. Compliance with the diet did not change during the follow-up. Conclusions. Large amounts of both unkilned and regular kilned oats are well tolerated by adult patients with CD. Oats is therefore not harmful, even in its unkilned form, which indicates that its antigenic nature is not changed by common industrial food processing in such a way that would prevent the provoking of CD.     

In vitro tests indicate that certain varieties of oats may be harmful to patients with coeliac disease

BACKGROUND: The presence of oats in gluten-free diet is controversial. The aim of this work is to evaluate if different varieties of oats exert different toxicity in coeliac disease. METHODS: Three varieties of oats were tested by two in vitro assay based on the known ability of peptic-tryptic digests of coeliac-active proteins to agglutinate K562 cells and to disrupt lysosomes, respectively. RESULTS: Avenins from the Italian variety Astra and the Australian variety Mortlook were much more active than the Australian variety Lampton. Gliadin, digested in the same way, certainly displayed more activity than all three avenins, but rice (var. Roma) did not have measurable activity. CONCLUSIONS: The results indicate that some varieties of oats may be potentially harmful to individuals with coeliac disease and therefore should be excluded from the gluten-free diet required to maintain good health in coeliac disease. It is important to realize that constant, small amounts of active proteins in the diet, such as certain avenins, may prevent complete recovery of the intestinal mucosa in this disease.     

Role of oats in celiac disease

A gluten-free diet is currently the only effective means of treating individuals with celiac disease. Such a diet enables celiac patients to control their symptoms and avoid various complications associated with thiscondition. However, while the quality of gluten-free foods has significantly improved during recent decades, maintenance of a gluten-free diet does not necessarily ensure adequate nutritional intake. Because oats are an important source of proteins, lipids, vitamins, minerals, and fibre, their inclusion in a gluten-free diet might improve the nutritional status of a celiac patient. Although oats are included in the list of glutenfree ingredients specified in European regulations, their safety when consumed by celiac patients remains debatable. Some studies claim that pure oats are safe for most celiac people, and contamination with other cereal sources is the main problem facing people with this disease. However, it is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet.     

Genetics in coeliac disease

Coeliac disease has a strong genetic component, higher than for many other common complex diseases. Possession of the HLA-DQ2 variant is required for presentation of disease causing dietary antigens to T cells, although this is also common in the healthy population. Non-HLA genetic factors account for the majority of heritable risk. Linkage studies have identified promising regions on chromosomes 5 and 19, with multiple other loci awaiting definitive confirmation in independent studies. Inherited variants in the tightly clustered chromosome 2q CD28-CTLA4-ICOS region are associated with disease, although of weak effect size. Larger sample sizes are necessary in coeliac disease genetic studies to detect small effects, alternatively meta-analysis offers promise. Newer methods including gene expression analysis and genome wide association studies will advance understanding of genetic susceptibility. Identification of coeliac disease genes may improve diagnostic/prognostic markers, basic understanding of disease aetiology, permit development of novel therapeutics and provide insight into other autoimmune disorders.     

Lymphadenopathy in coeliac disease

We present two cases of adult coeliac disease whose major clinical feature was marked lymphadenopathy. One patient also displayed a peripheral lymphocytosis which varied with treatment of the underlying disease.     

Risk of intestinal lymphoma in undiagnosed coeliac disease: Results from a registered population with different coeliac disease prevalence

BackgroundCoeliac disease is often undiagnosed, early diagnosis and treatment could be relevant to avoid fearful complications as intestinal lymphoma. Our aim is to estimate the risk of intestinal lymphoma in undiagnosed coeliac patients, evaluating the real incidences and applying different theoretical settings of coeliac prevalence.MethodsWe collected cases of intestinal lymphomas from the Lombardy Cancer Registry and coeliac patients through computerized search of all Pathology Departments; duodenal pathological reports compatible with a Marsh 3 grade were included. The lymphoproliferative risk was calculated for theoretical different settings of coeliac prevalence (from 1:50 to 1:200), relative risks for intestinal lymphomas and compared to the real incidence of the lymphomas in this population.ResultsPopulation consisted in 815,362 inhabitants; during the investigated period of time, 237 intestinal lymphomas and 326 coeliac patients were diagnosed. None of the coeliac patients had lymphoma. In the different scenarios calculated and compared with the real lymphoma incidence the relative risks of undiagnosed celiac disease for gastrointestinal B- and T-cell lymphomas ranges from 1.0 to 2.0 for 1:100 coeliac disease prevalence.ConclusionsUndiagnosed coeliac patients have no increased risk of developing intestinal lymphoma; population screening programmes, aimed at early diagnosis of lymphoma may not be useful in this setting.     

Persistent mucosal abnormalities in coeliac disease are not related to the ingestion of trace amounts of gluten.

BACKGROUND: It is expected that in patients with coeliac disease the small-bowel mucosal mucosa will return to normal if they adhere to a gluten-free diet (GFD). However, in many this is not the case. This study aims to determine whether this persistent villous atrophy (VA) could be due to continued ingestion of the trace amounts of gluten in 'gluten-free' foods, as defined by the WHO/FAO Codex Alimentarius. METHODS: Duodenal biopsy specimens from 89 adults with long-standing coeliac disease were examined, and the findings correlated with their form of gluten-free diet. RESULTS: In 51 subjects the duodenal specimen was normal, whereas in 38 there was villous atrophy (partial, 28; subtotal, 8; total, 2). There was no relationship between the presence or absence of VA and ingestion of either a GFD as defined by the Codex Alimentarius (Codex-GFD; 39 patients) or a GFD that contained no detectable gluten (NDG diet: 50 patients). Intraepithelial lymphocyte counts were higher, and lactase levels lower, in subjects with an abnormal biopsy specimen than in those in whom it was normal. However, within each of these biopsy groups there was no difference in these variables between patients on a Codex-GFD and those on an NDG-GFD. IgA antigliadin antibody was detected in 4 of 29 patients on a Codex-GFD and in 3 of 13 on a NDG-GFD (NS). CONCLUSION: The persistent mucosal abnormalities seen in patients with coeliac disease on a GFD are not due to the ingestion of trace amounts of gluten. The consequences of these abnormalities have yet to be determined.     

Coeliac disease autoantibodies in seminal plasma from cases with screen-detected coeliac disease

Morphological changes in the remnant mucosa 2–20 years after operation for duodenal ulcer (DU) were analyzed in 124 male subjects by means of stochastic mathematics. Fifty non-operated male DU patients and 168 age-matched males from a population sample served as controls. Substantially no progression of gastritis was found in the DU patients. In contrast, the operative intervention caused a rapid initial progression of gastritis, continuing after 2 years approximately at the same speed as in the population at large.