Celiac Disease and Sensitization to Wheat, Rye, and Barley: Should We Be Concerned?

BACKGROUND: Concomitance of celiac disease (CD) and IgE-mediated wheat allergy is described in some case reports. The objective was to evaluate the frequency of sensitization to wheat, rye, barley, and malt in children and adolescents with CD. METHODS: Measurement of serum levels of specific IgE to wheat, rye, barley, and malt (ImmunoCAP; sensitization IgE ≥0.35 kUA/L) in CD patients followed in specialized clinics to verify allergy history, general characteristics, small bowel biopsy characteristics, compliance with gluten-free diet (GFD), and occurrence of symptoms in case of noncompliance. RESULTS: We evaluated 74 patients; the median of age and age at diagnosis of CD were 8.6 years (5.0-12.8) and 3.6 years (1.6-7.0), respectively. Median time of GFD was 3.5 years (1.4-5.8). History of asthma occurred in 17.3% of subjects, allergic rhinitis in 13.5%, and AD in 5.4%. Frequency of sensitization was 4% for wheat, 10.8% for rye, 5.4% for barley, and 2.7% for malt. There was no association between wheat sensitization and age at diagnosis, time of GFD, small bowel biopsy characteristics, allergy history, and gluten consumption. There was no relationship between sensitization to wheat and occurrence of immediate symptoms when not complying with GFD. CONCLUSION: In conclusion, the frequency of sensitization to wheat, rye, barley, and malt in CD patients was 4, 10.8, 5.4, and 2.7%, respectively. Therefore, to ensure that cutaneous and respiratory contact with wheat is safe, we advise patients with CD to investigate their sensitivity to wheat, rye, and barley because not all patients with CD are allergic to these cereals.

Clinical and in vitro cross-reactivity of cereal grains in children with IgE-mediated wheat allergy.

INTRODUCTION AND OBJECTIVES: Wheat and cereal grains have a broad range of cross-reactivity, but the clinical relevance of this cross-reactivity is uncertain. This study aimed to evaluate clinical and in vitro cross-reactivity with barley, oat, and Job's tears among wheat-allergic patients. MATERIALS AND METHODS: Patients aged 5 to 15 years with IgE-mediated wheat allergy were enrolled. Skin prick test (SPT) and specific IgE (sIgE) to wheat, barley, and oat, and SPT to Job's tears were performed. Oral food challenge (OFC) was conducted if the SPT was ≤5 mm in size and there was no history of anaphylaxis to each grain. Profiles of sIgE bound allergens of wheat, barley, and oat, and inhibition ELISA of IgE binding to barley and oat with wheat were performed. RESULTS: Ten patients with a median age of 8 years were enrolled. Nine of those patients had a history of wheat anaphylaxis. The median SPT size and sIgE level to wheat was 7.3 mm and 146.5 kUA/l, respectively. The cross-reactivity rate for barley, oat, and Job's tears was 60.0%, 33.3%, and 20.0%, respectively. Significantly larger SPT size and higher sIgE level were observed in patients with positive cross-reactivity to barley and oat when compared to patients without cross-reactivity. Barley and oat extracts inhibited 59% and 16% of sIgE bound to wheat gliadins and glutenins, respectively. CONCLUSION: The cross-reactivity rate was quite low for oat and Job's tears compared to that of barley; therefore, avoidance of all cereal grains may be unnecessary in patients with severe wheat allergy.

Characterisation of clinical and immune reactivity to barley and rye ingestion in children with coeliac disease.

OBJECTIVE: Barley and rye are major components of the Western diet, and historic feeding studies indicate that they cause clinical effects in patients with coeliac disease (CD). This toxicity has been attributed to sequence homology with immunogenic wheat sequences, but in adults with CD, these cereals stimulate unique T cells, indicating a critical contribution to gluten immunity independent of wheat. Clinical and immune feeding studies with these grains in children with CD are sparse. We undertook a barley and rye feeding study to characterise the clinical and T-cell responses in children with CD. DESIGN: 42 children with human leucocyte antigen (HLA)-DQ2.5+ (aged 3-17 years) consumed barley or rye for 3 days. Blood-derived gluten-specific T cells were tested for reactivity against a panel of barley (hordein) and rye (secalin) peptides. Hordein and secalin-specific T-cell clones were generated and tested for grain cross-reactivity. T-cell receptor sequencing was performed on sorted single cells. T-cell responses were compared with those observed in adults with CD. RESULTS: 90% of the children experienced adverse symptoms, mostly GI, and 61% had detectable gluten-specific T-cell responses targeting peptides homologous to those immunogenic in adults. Deamidation was important for peptide reactivity. Homozygosity for HLA-DQ2.5 predicted a stronger T-cell response. Gluten-specific T cells showed striking similarities in their cross-reactivity between children and adults. CONCLUSIONS: Barley and rye induce a consistent range of clinical and T-cell responses in children with CD. The findings highlight the importance of a series of dominant hordein and secalin peptides pathogenic in children with CD, some independent of wheat, which closely correspond to those seen in adults.

Surgical treatment of awn aspiration causing bronchopleural fistula and bronchiectasis: case reports.

BACKGROUND: Aspiration of grass inflorescences is an extremely rare phenomenon with potential diagnostic difficulties. Due to its special shape, each coughing and respiratory action helps its migration towards the periphery of lung, resulting late-onset, life-threatening complications. The diagnosis has some difficulties for the reason that soon after the aspiration initial symptoms, such as coughing, wheezing or vomiting disappear and bronchoscopy is mostly negative. At least serious complications such as tension pneumothorax, bronchopleurocutaneous fistula or even spontaneous percutan elimination may develope. CASE PRESENTATION: We present two cases of pleuropneumonia resulting from aspiration of the head of barley grass. Soon after the accidents initial symptoms diminished, inflammatory markers improved and bronchoscopy was unable to confirm the presence of awn. Despite of conservative treatment (antibiotics, physiotherapy, bronchodilators, expectorants, and inhalation) localized pulmonary inflammation developed after 1 and 9 months showed up on chest computed tomography. After ineffective conservative treatment, surgical resections became inevitable in order to remove chronically inflamed parts (lobectomy, segmentectomy) and foreign bodies. Both patients recovered and were discharged home after successful interventions. CONCLUSIONS: Due to its peculiar shape and behaviour, awn inhalation is a special and atypical form of aspiration, thus great care and awareness is needed in its treatment. Negative bronchoscopic result does not exclude the presence of bronchial grass head. Symptomless child with negative bronchoscopy and improved inflammatory markers should be followed up thoroughly to recognize late complications in time. Regular diagnostic steps (chest ultrasound/X-ray) should be performed to localize potential chronic lung inflammation. Chest computed tomography is a valuable diagnostic tool for identifying and localising the foreign body. In cases with localized inflammation and peripheric localisation, segmentectomy can be a successful and safe alternative of lobectomy.

Amylase-Trypsin Inhibitors in Wheat and Other Cereals as Potential Activators of the Effects of Nonceliac Gluten Sensitivity.

Nonceliac gluten sensitivity (NCGS) is a gluten-related gastrointestinal disorder distinct from celiac disease (CD) and gluten allergy that is not easy to diagnose due to the lack of biomarkers. It is characterized by intestinal symptoms and extraintestinal manifestations with the consumption of gluten-containing foods. In contrast to CD, NCGS patients do not present a genetic predisposition or intestinal villi atrophy. Recent studies question the proinflammatory triggering activity of α-gliadin fraction contained in wheat, since it has been demonstrated that the amylase-trypsin inhibitors (ATIs) exert a strong activating effect on the innate immune response. We aimed to analyze the role of ATIs in the activation of innate immunity and in the development of the symptoms characteristic of NCGS. A systematic literature search was made using databases such as MEDLINE, SciELO, Science Direct, and Scopus, with focus on key words such as "amylase-trypsin inhibitors," "wheat," "gluten," and "celiac." Many studies are available on the structure, inhibition mechanism, and immune system effects of ATIs, mainly focused on IgE-mediated reactions. Recently, with the increase of NCGS interest, has increased the literature on the capacity of ATIs contained in wheat to activate the innate immune system. Literature published to date questions the relationship between activation of the innate immune system and gluten in NCGS. ATIs may have acted as interfering contaminant of gluten and appear as potential activator of innate immunity in NCGS patients. In view of their potential impact, more interventional studies are needed to demonstrate the proinflammatory effect of ATIs.

Adverse Effects of Wheat Gluten.

Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet.

Evaluation through literature data on standardized ileal digestibility and basal ileal endogenous loss of amino acids associated with barley in pigs.

This meta-analysis aimed to estimate the standardized ileal digestibility (SID) and the basal ileal endogenous amino acid losses (IAAend) in barley for growing pigs. In total, 38 different barley treatments published in 26 peer-reviewed papers were used for the meta-analysis containing information on dietary composition including amino acid (AA) contents of the assay diets, and (or) barley samples, as well as apparent ileal digestibility (AID) of AA in barley. The SID of AA was determined by either correcting AID of AA for their IAAend or by regression analysis between the apparent ileal digestible and total dietary AA contents. The SID values obtained by correcting the AID values for their IAAend amounted to 70%, 77%, 74% and 63% for Lys, Met, Thr and Trp, whereas those based on regression analysis method were 82%, 82%, 69% and 55%, respectively. Estimates of basal ileal endogenous loss of CP in ileal digesta varied considerably and averaged 11.84 g/kg dry matter intake (DMI), whereas IAAend for indispensable AA ranged from 0.05 g/kg DMI for Trp to 1.90 g/kg DMI for Leu. In most cases, these estimates were considerably higher than previously reported values for IAAend. The results of the present regression analysis indicate for most AA higher SID values compared with SID of most AA that were obtained by correcting AID values for IAAend. In view of the observed high variations in IAAend and the low CP content of the barley samples, estimating SID of AA based on literature data by means of the regression method may improve accuracy of SID coefficients for barley. In contrast, transformation of AID values into their corresponding SID values by using a constant correction factor for IAAend adds an additional source of error, thereby reducing the precision in estimating SID of AA.

Feeding barley grain-rich diets altered electrophysiological properties and permeability of the ruminal wall in a goat model.

High-producing ruminants are commonly fed large amounts of concentrate to meet their high energy demands for rapid growth or high milk production. However, this feeding strategy can severely impair rumen functioning, leading to subacute ruminal acidosis. Subacute ruminal acidosis might have consequences for electrophysiological properties by changing the net ion transfer and permeability of ruminal epithelia, which may increase the uptake of toxic compounds generated in the rumen into the systemic circulation. The objective of the present study was to investigate the effects of excessive barley feeding on the electrophysiological and barrier functions of the ruminal epithelium and serum inflammation and ketogenesis markers after a long-term feeding challenge, using growing goats as a ruminant model. A feeding trial was carried out with growing goats allocated to 1 of the 3 groups (n=5-6 animals/group), with diets consisting exclusively of hay (control diet) or hay with 30 or 60% barley grain. Samples of the ventral ruminal epithelium were taken after euthanasia and instantly subjected to Ussing chamber experiments, where electrophysiological properties of the epithelium were measured in parallel with the permeability of marker molecules of different sizes [fluorescein 5(6)-isothiocyanate and horseradish peroxidase] from luminal to apical side. Additionally, ruminal fluid and blood samples were taken at the beginning of the experiment as well as shortly before euthanasia. Ruminal fluid samples were analyzed for volatile fatty acids and pH, whereas blood samples were analyzed for lipopolysaccharide, serum amyloid A, and ß-hydroxybutyrate. Electrophysiological data indicated that barley feeding increased the epithelial short-circuit current compared with the control. Tissue conductance also increased with dietary barley inclusion. As shown with both marker molecules, permeability of ruminal epithelia increased with barley inclusion in the diet. Despite a lowered ruminal pH associated with increased volatile fatty acids (such as propionate and butyrate) concentrations as well as altered epithelial properties in response to high-grain feeding, no signs of inflammation became apparent, as blood serum amyloid A concentrations remained unaffected by diet. However, greater amounts of grain in the diet were associated with a quadratic increase in lipopolysaccharide concentration in the serum. Also, increasing the amounts of barley grain in the diet resulted in a tendency to quadratically augment serum concentrations of ß-hydroxybutyrate and, hence, the alimentary ketogenesis. Further studies are needed to clarify the role of barley inclusion in the development of subacute ruminal acidosis in relation to ruminal epithelial damage and the translocation of toxic compounds in vivo.

Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4.

Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an ill-defined component of innate immunity in celiac disease. We identify the α-amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4-MD2-CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients' biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.

Significant differences in coeliac immunotoxicity of barley varieties.

SCOPE: The only treatment available for coeliac disease (CD) is a strict diet in which the intake of wheat, barley, rye, or oats is avoided. Barley is a major cereal crop, grown mainly for its use in brewing, and it has high nutritional value. The identification of varieties with a reduced toxicity profile may contribute to improve the diet, the quality of life and health of CD patients. METHODS AND RESULTS: Searching for harmless barleys, we investigated accessions of malting and wild barley, used for developing new cultivated cereals. The CD toxicity profile of barleys was screened using G12 antibody and cell proliferation and IFN-γ release from peripheral blood mononuclear cells and intestinal biopsies from CD patients. We found a direct correlation between the reactivity with G12 and the immunogenicity of the different barleys. CONCLUSION: The malting barleys were less immunogenic, with reduced levels of toxic gluten, and were possibly less harmful to CD patients. Our findings could raise the prospect of breeding barley species with low levels of harmful gluten, and the attractive goal of developing nontoxic barley cultivars, always taking into account the Codex standard for foods for special dietary use for persons intolerant to gluten.

Mouse barley awn (Hordeum murinum) migration induced cystolithiasis in 2 male dogs.

Two male dogs were presented with cystic uroliths composed of magnesium ammonium phosphate (struvite). Each had an atypical nidus, a mouse barley awn (Hordeum murinum). To our knowledge, this is the first report of grass awns located in the bladder lumen of dogs. The composition of uroliths and the pathophysiology of grass awn migration to the urinary bladder are discussed.

Safety of barley starch syrup in patients with allergy to cereals.

It is not known whether trace amounts of proteins that may remain in cereal-starch-derived food ingredients even after food processing can trigger allergic symptoms in cereal-allergic individuals. The aim of this study was to find out if barley starch syrup causes allergic reactions in patients with allergy to wheat, barley, rye or oats. Fifteen children with allergy to these cereals, confirmed by double-blind placebo-controlled food challenge (DBPCFC), were selected for the study. When exposed to cereals, seven of the children (47%) showed immediate type reactions, such as urticaria, rash or anaphylaxis. Eight of the children (53%) showed delayed type reactions, such as deterioration of atopic dermatitis or diarrhoea. The fifteen children with allergy to cereals were exposed to barley starch syrup in DBPCFC and none of them showed any objective signs of allergy. On skin-prick tests (SPT), five of the children (33.3%) showed a positive (>or= 3 mm) reaction to at least one of the cereals but none of them to barley starch syrup. This study confirmed with 98% confidence that at least 90% of the patients with verified allergy to cereals will not react with allergic symptoms to barley starch syrup.

Severe thiamine deficiency in sheep with acute ruminal lactic acidosis.

BACKGROUND: Thiamine status of ruminants is adversely affected in acidic rumen conditions. However, there have been limited published case study data related to thiamine deficiency of ruminants with acute ruminal lactic acidosis (ARLA). HYPOTHESIS: Thiamine deficiency would occur in sheep with ARLA. ANIMALS: Thirteen Ak-Karaman (white Karaman) sheep with ARLA, aged 1 year (ARLA group) and 10 healthy Ak-Karaman sheep, aged 1 year (control group) were used. METHODS: After clinical examination, rumen fluid samples of all sheep were obtained with a stomach tube and examined immediately. Blood samples were taken from a jugular vein of the sheep. Erythrocytic transketolase enzyme activity and hence thiamine pyrophosphate (TPP) effect were determined according to Clausen's method. RESULTS: History revealed that all sheep in the ARLA group had accidentally consumed excessive amounts of cracked barley. During clinical examination of the ARLA group, disturbed general condition, engorged scleral vessels, moderate to severe dehydration, and ruminal atony were recorded in the sheep. The results of the ruminal fluid analyses of the ARLA group demonstrated characteristics of ARLA. The results of clinical and ruminal fluid examination of control group were normal. The mean TPP effect (%) in the ARLA group (109 +/- 28) was significantly higher than in the control group (22.2 +/- 3.7) (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The present study revealed that severe thiamine deficiency occurred in sheep with ARLA. This result indicates that thiamine administration to sheep suffering from acute ruminal acidosis caused by overconsumption of readily fermentable carbohydrates could be beneficial in alleviating thiamine deficiency caused by ruminal acidosis.

Polioencephalomalacia in cattle: a consequence of prolonged feeding barley malt sprouts.

Polioencephalomalacia (PEM) in ruminants has been recognized as a consequence of excess sulphur intake. The present study describes clinical, gross and histopathological findings of PEM following an abrupt change of diet in two ranches housing 2750 dairy and 2300 beef cattle. As a result of severe PEM, 256 cattle died or were slaughtered. Clinical findings included circling, hypersensitivity, excessive salivation, hypermetria, incoordination, blindness and death. The first clinical signs occurred in beef calves (6-8 months old) at a holding facility. Clinical signs of the disorder continued intermittently during the 5-month period in both ranches and were more evident in calves and lactating dairy cows. The affected cattle did not respond to thiamine injections. Clinical signs disappeared gradually following removal of barley malt sprouts from the diet. Although macroscopic lesions were not apparent in the brain tissues of some animals, histopathology typical of PEM was found in most cases: spongiosis in the neuropil and neuronal necrosis, haemorrhage, capillary hyperplasia, fibrinoid degeneration in arterioles, multifocal liquefaction necroses in the grey matter and abundance of gitter cells with vacuolar large cytoplasm. Sulphide in rumen fluid of a clinically affected animal was measured as 1.55 mg/dl, which is considerably higher than that collected from two control cows (mean 0.21 mg/dl). The total sulphur content of the diet containing barley malt sprouts was estimated to be 0.45%, which is also higher than the National Research Council (NRC) maximum tolerable levels. In conclusion, PEM can result from excess barley malt sprout intake because of its higher sulphur content. Clinical signs may occur shortly after the intake of barley malt sprout as outbreaks with a higher number of deaths or as an ongoing periodic condition.