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.

Baker's Asthma: Is the Ratio of Rye Flour-Specific IgE to Total IgE More Suitable to Predict the Outcome of Challenge Test Than Specific IgE Alone.

Usually the diagnosis of baker's asthma is based on specific inhalation challenge with flours. To a certain extent the concentration of specific IgE to flour predicts the outcome of challenge test in bakers. The aim of this study was to evaluate whether the ratio of specific IgE (sIgE) to total IgE (tIgE) improves challenge test prediction in comparison to sIgE alone. Ninety-five bakers with work-related respiratory symptoms were challenged with rye flour. Total IgE, sIgE, and the sIgE/tIgE ratio were determined. Receiver operator characteristic (ROC) plots including the area under the curve (AUC) were calculated using the challenge test as gold-standard. Total IgE and sIgE concentrations, and their ratio were significantly higher in bakers with a positive challenge test than in those with a negative one (p < 0.0001, p < 0.0001, and p = 0.023, respectively). In ROC analysis, AUC was 0.83 for sIgE alone, 0.79 for tIgE, and 0.64 for the ratio. At optimal cut-offs, tIgE, sIgE, and the ratio reached a positive predicted value (PPV) of 95%, 84% and 77%, respectively. In conclusion, calculating the ratio of rye flour-sIgE to tIgE failed to improve the challenge test prediction in our study group.

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.

Sensitization to xylanolytic enzymes: an underestimated health hazard among bakers.

BACKGROUND: The most important occupational allergens in baking include flour and enzymes, especially α-amylase. Although xylanolytic enzymes have previously been described as sensitizers, they may be overlooked during assessment of bakery workers with work-related symptoms. AIMS: To report a case of a baker who suffered from work-related respiratory, ocular and skin symptoms as a consequence of sensitization to xylanolytic enzymes. METHODS: Physical examination, chest X-ray, routine laboratory tests, skin prick tests (SPTs) with common and occupational allergens (wheat, pearl, rye, corn and oat flours, α-amylase, bakery adjuvants) and spirometric measurements, as well as assessments by a laryngologist, dermatologist and ophthalmologist were performed. Specific IgE (sIgE) to occupational agents were evaluated for flours, α-amylase, xylanase, cellulose and glucoamylase. Specific inhalation challenges (SICs) with flours and bakery adjuvants were carried out. RESULTS: Hypersensitivity to Aspergillus moulds, flours and α-amylase was confirmed in SPTs; however, SIC with those agents gave a negative result. Further investigation revealed the presence of sIgE to xylanolytic enzymes. During SIC with bakery adjuvants, allergic skin, ocular and respiratory symptoms occurred and were confirmed by objective assessment. CONCLUSIONS: In the assessment of work-related allergic symptoms in bakers, sensitization to xylanolytic enzymes should be considered. Completion of diagnostic procedures having excluded asthma and rhino-conjunctivitis related to flour hypersensitivity might result in a false-negative assessment.

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.

Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women--a randomized control trial.

BACKGROUND: Epidemiological studies have consistently shown that whole grain (WG) cereals can protect against the development of chronic diseases, but the underlying mechanism is not fully understood. Among WG products, WG rye is considered even more potent because of its unique discrepancy in postprandial insulin and glucose responses known as the rye factor. In this study, an NMR-based metabolomics approach was applied to study the metabolic effects of WG rye as a tool to determine the beneficial effects of WG rye on human health. METHODS: Thirty-three postmenopausal Finnish women with elevated serum total cholesterol (5.0-8.5 mmol/L) and BMI of 20-33 kg/m² consumed a minimum of 20% of their daily energy intake as high fiber WG rye bread (RB) or refined wheat bread (WB) in a randomized, controlled, crossover design with two 8-wk intervention periods separated by an 8-wk washout period. At the end of each intervention period, fasting serum was collected for NMR-based metabolomics and the analysis of cholesterol fractions. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. RESULTS: The metabolomics analysis of serum showed lower leucine and isoleucine and higher betaine and N,N-dimethylglycine levels after RB than WB intake. To further investigate the metabolic effects of RB, the serum cholesterol fractions were measured. Total- and LDL-cholesterol levels were higher after RB intake than after WB (p<0.05). CONCLUSIONS: This study revealed favorable shifts in branched amino acid and single carbon metabolism and an unfavorable shift in serum cholesterol levels after RB intake in postmenopausal women, which should be considered for evaluating health beneficial effects of rye products.

Dietary supplements for benign prostatic hyperplasia: an overview of systematic reviews.

Benign prostatic hyperplasia (BPH) is a common chronic condition in older men. The aim of this overview of systematic reviews (SRs) is to summarise the current evidence on the efficacy and adverse effects of dietary supplements for treating BPH with lower urinary tract symptoms. We searched 5 electronic databases and relevant overviews without limitations on language or publication status. Six SRs of 195 articles were included in this overview. Serenoa repens was reviewed in 3 studies and no specific effect on BPH symptoms and urinary flow measures was observed. However, ß-sitosterol, Pygeum africannum and Cernilton were reviewed in one study each, and significant improvement was observed for all three. All the included compounds have mild and infrequent adverse effects. SRs on ß-sitosterol, Pygeum africannum and Cernilton have not been updated since 2000, thus an update of reviews on these compounds will be necessary in the future.

Maternal antenatal peanut consumption and peanut and rye sensitization in the offspring at adolescence.

BACKGROUND: There is considerable controversy whether maternal peanut ingestion during pregnancy might influence sensitization in later life. Objective To examine whether maternal peanut ingestion during pregnancy might increase sensitization in the offspring. METHODS: A population-based longitudinal cohort study with 16 years follow-up was conducted (N=373). Subjects were recruited at birth as part of an infant health study. Maternal antenatal peanut consumption was documented at birth and peanut and rye sensitization were determined by measurement of serum-specific IgE at age 16. RESULTS: Peanut sensitization was common (14%). In the entire cohort (n=310), there was no association between antenatal peanut ingestion and peanut sensitization (P=0.17). However, there was a strong association between antenatal peanut ingestion and decreased risk of rye sensitization and peanut sensitization in those (n=201) without a family history (FH) of asthma (Rye OR 0.30, 95% CI 0.14-0.63, P=0.001 and Peanut OR 0.18, 95% CI 0.04-0.78, P=0.02). There was an increased risk of rye sensitization in those (n=108) with a FH of asthma and antenatal peanut ingestion (Rye OR 2.69, 95% CI 1.11-6.51 P=0.03). It was considered that these sensitizations were likely to be related to the presence of IgE antibodies to cross-reacting carbohydrate epitopes common to rye and peanut allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Antenatal peanut ingestion may influence the development of IgE antibody to cross-reacting carbohydrate epitopes in later life. Genetic factors may modify this association.

[A comparative clinical randomized trial of cernilton efficacy and safety in patients with chronic abacterial prostatitis].

The trial of efficacy and safety of two doses of the drug cernilton in patients with chronic abacterial prostatitis made in the Research Institute of Urology and I.M. Sechenov Medical Academy in 2008 gave evidence for subjective (NIH-CPSI, Sex-4, IPSS and other scales, QOL) and objective (leucocyte count in prostatic secretion) pronounced anti-inflammatory effects of the drug which persist for at least 6 months. Comparison of the two doses of cernilton showed significant differences in subjective response of the patients (NIH-CPSI and Symptom Frequency Scale). Cernilton is recommended as a medication of choice for treatment of patients with chronic abacterial prostatitis.

Determinants of asthma phenotypes in supermarket bakery workers.

While baker's asthma has been well described, various asthma phenotypes in bakery workers have yet to be characterised. Our study aims to describe the asthma phenotypes in supermarket bakery workers in relation to host risk factors and self-reported exposure to flour dust. A cross-sectional study of 517 supermarket bakery workers in 31 bakeries used a questionnaire, skin prick tests, and specific immunoglobulin E to wheat, rye and fungal alpha-amylase and methacholine challenge testing. The prevalence of probable occupational asthma (OA, 13%) was higher than atopic (6%), nonatopic (6%) and work-aggravated asthma (WAA, 3%) phenotypes. Previous episodes of high exposure to dusts, fumes and vapours causing asthma symptoms were more strongly associated with WAA (OR 5.8, 95% CI 1.7-19.2) than OA (2.8, 1.4-5.5). Work-related ocular-nasal symptoms were significantly associated with WAA (4.3, 1.3-13.8) and OA (3.1, 1.8-5.5). Bakers with OA had an increased odds ratio of reporting adverse reactions to ingested grain products (6.4, 2.0-19.8). OA is the most common phenotype among supermarket bakery workers. Analysis of risk factors contributes to defining clinical phenotypes, which will guide ongoing medical surveillance and clinical management of bakery workers.

The interaction between early life upper respiratory tract infection and birth during the pollen season on rye-sensitized hay fever and ryegrass sensitization--a birth cohort study.

Studies on early life viral respiratory infection and subsequent atopic disease in childhood have conflicting findings. Animal models show that viral respiratory infection in conjunction with allergen presentation can enhance sensitization. This prospective study assesses the influence of an upper respiratory tract infection (URI) in the first month of life and the season of birth on the development of hay fever and ryegrass allergen sensitization in childhood. From a Tasmanian cohort born during 1988 and 1989, a group of 498 children were followed up at 8 yr and another different group of 415 children were followed up at 16 yr. The ryegrass pollen season in Tasmania occurs in November and December. Forty-four (9.6%) children in Follow-up sample 1 and 47 (12.5%) children in Follow-up sample 2 were born in the pollen season. The parental report of an early upper respiratory tract infection (EURI) was documented prospectively by a home interview at 1 month of age (median age 5.1 wk). Sensitization to ryegrass and house dust mite (HDM) was determined at 8 yr of age by skin prick testing and at 16 yr by ImmunoCap. Ryegrass sensitized hay fever was defined as a positive response to a question on hay fever plus the presence of ryegrass allergy. For children tested at age 8 and born in the pollen season, a EURI by postnatal interview was associated with an increased risk of ryegrass sensitization (OR 5.80 95% CI 1.07, 31.31) but not for children with a EURI born outside the pollen season (OR 0.62 95% CI 0.35, 1.08). Similarly, EURI was significantly associated with early onset (< or = 8 yr) ryegrass sensitized hay fever for children born in the pollen season (AOR 4.78 95% CI 1.17, 19.47) but was not associated with early onset ryegrass sensitized hay fever for children born outside the pollen season (AOR 0.76 95% CI 0.43, 1.33). These findings suggest that early life viral URI interacts with ryegrass allergen exposure in the development of ryegrass allergen sensitization and ryegrass sensitized hay fever symptoms.

Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers.

BACKGROUND: Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours. AIMS OF THE STUDY: To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. METHODS: Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. RESULTS: Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. CONCLUSION: High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.

[Use of cernilton in the therapy of prostatic adenoma and chronic prostatitis].

Cernilton is a phytodrug containing pollen extract. It has antiandrogenic and anti-inflammatory effects influencing alpha1-adrenoblockers located in the zone of the detrusor and urethra. A conservative therapy with cernilton was given to 72 patients with chronic prostatitis and prostatic adenoma of stage I-II. Detailed urologic examination before the treatment and after it demonstrates that cernilton is effective, safe and well tolerated medicine for prostatic adenoma and chronic prostatitis. Cernilton is recommended for wider use in the treatment of patients with prostatic adenoma and chronic prostatitis.

Barley and rye prolamins induce an mRNA interferon-gamma response in coeliac mucosa.

BACKGROUND: In coeliac disease, wheat, barley and rye are traditionally excluded in the gluten-free diet. However, few studies have examined the small intestinal immune response to barley and rye. AIM: To investigate the immunogenicity of barley and rye prolamins (hordein and secalin respectively) in comparison with wheat gliadin. METHODS: Duodenal biopsies from 22 coeliac patients and 23 disease controls were cultured for 4 h with gliadin, hordein or secalin and compared with culture medium alone. Proinflammatory cytokines, interferon-gamma and interleukin-2, were quantified by TaqMan polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Hordein caused the greatest increase in interferon-gamma mRNA in coeliac patients (median: 3.3-fold) in comparison with control subjects (median: 0.28-fold, P < 0.085). Secalin and gliadin induced similar levels of interferon-gamma mRNA with median fold-changes of 3.4 and 2.8, respectively, in coeliac patients in comparison with 1.6- and 1.1-fold increases in control subjects (P < 0.294 and P < 0.105, respectively). The median fold-changes for interleukin-2 mRNA did not differ between coeliac patients and controls. Cytokine protein was not upregulated. CONCLUSION: The findings of this study provide evidence that barley and rye cause immune activation in the mucosa of coeliac patients and support the practice that barley and rye should be excluded from the gluten-free diet.

Cereal-induced anaphylaxis in an adult after eating a baby cereal formula.

Ingestion of infant cereal formula as a cause of anaphylaxis has been exclusively described in children. We report the case of a man who experienced an anaphylactic reaction after eating his son's cereal formula. We believe that cereals constitute a rising problem and a hidden allergen that can cause severe reactions. Although these reactions are not fully understood, they may possibly be a life-long event.

Occupational asthma: a case of Baker's asthma.

Asthma is one of the most prominent respiratory diseases worldwide. It is defined by airflow limitation and/or airway hyperresponsiveness and can be exacerbated by a number of environmental allergens. When allergic asthma exacerbations are attributed to stimuli in a particular work environment, then occupational asthma must be considered. Incidence estimates vary, but in 1999 the Surveillance of Work-Related and Occupational Respiratory Disease in the United Kingdom estimated 4293 incident cases of occupational respiratory disease, an increase of 1427 cases over the previous year. Occupational asthma represented 26% of these cases. Baker's asthma is one of the most frequently reported types of occupational asthma in several countries. Diagniostic steps include thorough history, careful exam, and demonstration of functional reversible airflow obstruction. Treatment modalities used for occupational asthma are similar to those used in the management of other forms of asthma, with particular attention to reducing the level of exposure to the inciting allergen.

Characterization of cereal toxicity for celiac disease patients based on protein homology in grains.

BACKGROUND AND AIMS: Celiac disease is caused by T-cell responses to wheat gluten-derived peptides. The presence of such peptides in other widely consumed grains, however, has hardly been studied. METHODS: We have performed homology searches to identify regions with sequence similarity to T-cell stimulatory gluten peptides in the available gluten sequences: the hordeins of barley, secalins of rye, and avenins of oats. The identified peptides were tested for T-cell stimulatory properties. RESULTS: With 1 exception, no identical matches with T-cell stimulatory gluten peptides were found in the other grains. However, less stringent searches identified 11 homologous sequences in hordeins, secalins, and avenins located in regions similar to those in the original gluten proteins. Seven of these 11 peptides were recognized by gluten-specific T-cell lines and/or clones from patients with celiac disease. Comparison of T-cell stimulatory sequences with homologous but non-T-cell stimulatory sequences indicated key amino acids that on substitution either completely or partially abrogated the T-cell stimulatory activity of the gluten peptides. Finally, we show that single nucleotide substitutions in gluten genes will suffice to induce these effects. CONCLUSIONS: These results show that the disease-inducing properties of barley and rye can in part be explained by T-cell cross-reactivity against gluten-, secalin-, and hordein-derived peptides. Moreover, the results provide a first step toward a rational strategy for gluten detoxification via targeted mutagenesis at the genetic level.