Prediction of sensitization to flour allergens

The purpose of the present study was to investigate the factors that may contribute to the sensitization to flour in baker's apprentices, and to predict this type of sensitization with a stepwise logistic regression model. Of the total of 258 baker's apprentices, 54 (20.9%) exhibited specific IgE development against flour allergens (wheat, rye, and/or barley). Allergologic variables, such as the total IgE level and IgE specific to grass pollen, tree pollen, weed pollen, molds, and animal dander, were found to correlate strongly with the sensitization to flour. However, the correlation between the presence of other manifest allergies and the sensitization to flour was weak. The presence of shadowing of the paranasal sinuses on the radiograph (mucosal thickening, opacity, air/fluid levels, and/or polypous shadowing) correlated with flour sensitization as well as with the leukocyte and lymphocyte counts in peripheral blood. Of the lung function data, only total lung capacity (in percentage of the predicted values) weakly correlated with the sensitization to flour. We were able to predict flour sensitization with a sensitivity of 63%, a specificity of 90%, and an efficiency of 84% by using the parameters that allow for the presence or absence of IgE specific to grass pollen and tree pollen, the presence or absence of radiographic shadowing, and total lung capacity in percentage of the predicted values.     

Comparison of wheat and rye flour skin prick test solutions for diagnosis of baker's asthma

BACKGROUND: Skin prick tests (SPTs) play an important role in the diagnosis of baker's asthma and in the investigation of sensitization frequencies in field studies. It was the aim of our study to compare different SPT solutions for wheat and rye flour sensitization and to assess the validity of test results. METHODS: Skin prick tests with wheat and rye flour were performed in parallel with extracts from different companies and compared with the results of bronchial challenge tests with both flours (69 rye flour and 51 wheat flour challenge tests). Additionally, specific immunoglobulin E (sIgE) to wheat and rye flour were tested. SPT solutions were analysed for protein content and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Skin prick test solutions for diagnosis of wheat and rye flour sensitization from three companies differed in protein concentrations and composition with the consequence of widely differing SPT results. Sensitivity of SPTs in comparison with allergen-specific bronchial challenge as a gold standard was between 40 and 67%, specificity was between 86 and 100%, the positive predictive value (PPV) ranged from 81 to 100% and the negative predictive value (NPV) from 44 to 70%. These numbers were only marginally affected by using a combination of challenge test result and sIgE value as a more specific gold standard. CONCLUSION: Improvement and standardization of SPT extracts for wheat and rye flour is highly recommended.     

Clinical significance of IgG subclass antibodies to wheat flour antigens in bakers

We measured the IgG subclass antibody levels to wheat flour in 42 bakers and 20 controls with an enzyme immunoassay. The levels of total IgG, IgG1 IgG2 and IgG4 antibodies were significantly higher in the bakers than in the unexposed controls. The presence of anti-wheat flour IgG subclass antibodies in the bakers was correlated with various clinical variables including IgE levels, duration of asthmatic or rhinitis symptoms, skin prick test response, peripheral blood eosinophil levels, bronchial histamine reactivity and responses to nasal challenge with wheat flour. The IgG subclass antibody levels of the total cohort of bakers did not correlate with any of the measured clinical variables. However, among men specific IgG4 and IgG1 antibody levels correlated negatively with total IgE levels and duration of rhinitis, respectively. We conclude that IgG and IgG subclass levels to wheat flour in bakers reflect exposure, but that it is not related to any specific clinical situation. The exact pathogenic role of these antibodies in the development of occupational asthma and rhinitis is thus not clear.     

Clinical presentation,allergens, and management of wheat allergy

IgE-mediated allergy to wheat proteins can be caused by exposure through ingestion, inhalation, or skin/mucosal contact, and can affect various populations and age groups. Respiratory allergy to wheat proteins is commonly observed in adult patients occupationally exposed to flour, whereas wheat food allergy is more common in children. Wheat allergy is of growing importance for patients with recurrent anaphylaxis, especially when exercise related. The diagnosis of wheat allergy relies on a consistent clinical history, skin prick testing with well-characterized extracts and specific IgE tests. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several wheat components. However, a high degree of heterogeneity has been found in the recognition pattern of allergens among patient groups with different clinical profiles, as well as within each group. Thus, oral provocation with wheat or the implicated cereal is the reference test for the definitive diagnosis of ingested wheat/cereal allergy.     

Food allergy to wheat: identification of immunogloglin E and immunoglobulin G-binding proteins with sequential extracts and purified proteins from wheat flour.

BACKGROUND: Cereal-associated allergy is particularly considered a serious problem, because cereals are essential in our daily diet. Wheat proteins are classified into albumins, globulins and prolamins (insoluble gliadins and glutenins). OBJECTIVES: Our objectives were to study the involvement in food allergy to wheat of these different protein types by using purified fractions and to identify those binding IgE and IgG antibodies. METHODS: Sera were obtained from 28 patients with food allergy to wheat. Albumins/globulins, gliadins and glutenins were obtained by sequential extraction based on differential solubility; alpha-, beta-, gamma- and omega-gliadins and low molecular weight (LMW) and high molecular weight (HMW) glutenin subunits were purified by chromatography. IgE binding to these extracts and fractions were analysed by radioallergosorbent test (RAST), and immunoblotting; IgG binding was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: In RAST, 60% of sera were shown to have specific IgE antibodies against alpha-, beta-gliadins and LMW glutenin subunits, 55% to gamma-gliadins, 48% to omega-gliadins and 26% to HMW glutenins. Immunoblotting analysis confirmed results obtained in RAST concerning LMW and HMW glutenin subunits and showed that 67% of patients have IgE antibodies to the albumin/globulin fraction. CONCLUSION: Results obtained in the different tests showed common features and in agreement with other studies indicated the presence of numerous allergens in food allergy to wheat; alpha-, beta-, gamma- and omega-gliadins, LMW glutenin subunits and some water/salt-soluble proteins appeared as major IgE binding allergens, whereas HMW glutenins were only minor allergens. The same type of antigenic profile against gliadins and glutenins was observed with IgG antibodies. Important sequence or structural homologies between the various gliadins and LMW glutenin subunits could certainly explain similarity of IgE binding to these proteins.     

Immunoglobulin‐E‐binding epitopes of wheat allergens in patients with food allergy to wheat and in mice experimentally sensitized to wheat proteins

Background At present, B cell epitopes involved in food allergy to wheat are known only for a few allergens and a few categories of patients. Objective To characterize the epitopes of different wheat kernel allergens: α‐, γ, ω2, and ω5‐gliadin, a low‐molecular‐weight (LMW) glutenin subunit, and a lipid transfer protein (LTP1) recognized by allergic patients and by sensitized mice and provide further understanding of the role of structure in determining allergic response. Methods Sera were obtained from 39 patients suffering from food allergy to wheat. BALB/c mice were sensitized to gliadins or LTP1 by intraperitoneal immunizations. Continuous epitopes bound by IgE were delineated by the Pepscan technique. The response to reduced, alkylated LTP1 was compared with that of the native form to evaluate the importance of protein folding on IgE reactivity. Results Few continuous epitopes of LTP1 reacted with IgE from allergic patients and mice, but one of them was common to several patients and sensitized mice. The unfolded protein was not recognized by either patient or mouse IgE, emphasizing the major role of LTP1 folding and discontinuous epitopes in IgE‐binding. In contrast, many continuous epitopes were detected by patient and mouse IgE especially for an ω5‐gliadin, which is an unstructured protein, and to a lesser extent, for the other gliadins and a LMW‐glutenin subunit. Conclusion and Clinical Relevance The conformation of LTP1 appeared to have a strong impact on the type of IgE‐binding epitopes elicited by this protein in both man and mouse. The responses in mice sensitized to gliadins or LTP1 were sufficiently comparable with the human response in terms of IgE‐binding epitopes to provide support for the use of the mouse model in further investigations. Cite this as: S. Denery‐Papini, M. Bodinier, F. Pineau, S. Triballeau, O. Tranquet, K. Adel‐Patient, D.A. Moneret‐Vautrin, B. Bakan, D. Marion, T. Mothes, H. Mameri and D. Kasarda, Clinical & Experimental Allergy, 2011 (41) 1478–1492.     

Rye flour induces a stronger early bronchial response than wheat flour in occupational asthma

BACKGROUND: Our aims were to compare the doses of wheat and rye flour that induce early bronchial responses in occupationally exposed asthmatic subjects and to assess the effects of the dose of inhaled flour, the duration of exposure and the dose rate. METHODS: Ten patients underwent tests with lactose, wheat flour and rye flour. We compared the decrease in forced expiratory volume in 1 s (FEV(1)) observed during the challenge with flour and with lactose. We also calculated the amount of flour that was instantaneously active. RESULTS: Seven subjects had significantly decreased FEV(1) values following exposure to wheat and rye flour and two subjects only did so for rye flour. The provocative dose (PD, dose required to reduce FEV(1) by 15%) of rye was lower than that of wheat flour (geometric mean; PD(15) rye: 95 microg; wheat: 368 microg). The calculated doses of rye and wheat flour were better correlated with the change in FEV(1) than were the cumulative doses. CONCLUSION: The bronchial response was greater with rye than with wheat flour. The response was related to the dose of allergen inhaled and to the dose rate.     

Prevalence of self-reported food allergy in American adults and use of food labels

BACKGROUND: Few population-based studies in the United States have determined the prevalence of food allergy in adults and the problems these individuals might have with reading food labels. OBJECTIVE: The objectives of this study are to report the prevalence of self-reported food allergy, to identify the characteristics of food allergy reactions, and to describe the use of labels among adults with food allergy. METHODS: Questions from the US Food and Drug Administration's 2001 Food Safety Survey were analyzed to determine the prevalence of food allergy and opinions about food labels in the management of food allergy. RESULTS: The prevalence of self-reported food allergy is 9.1% among all survey respondents, with 5.3% of all respondents reporting a doctor-diagnosed food allergy. The prevalence of food allergy to the 8 most common allergens (peanut, tree nuts, egg, milk, wheat, soybeans, fish, and crustacean shellfish) is self-reported as 2.7% among respondents with doctors' diagnoses. Several label issues, such as words on some ingredient lists being too technical or hard to understand and food labels not always alerting persons to new ingredients, were reported as serious or very serious obstacles for managing an allergy. CONCLUSION: The prevalence of self-reported doctor-diagnosed food allergy among US adults is 5.3%, and a large portion of adults with food allergy found certain label issues a serious problem for managing their food allergy. CLINICAL IMPLICATIONS: The findings provide a needed source of population-based prevalence data of food allergy among US adults. Label issues identified are useful in understanding the difficulties of managing a food allergy.     

Occupational asthma and food allergy due to carmine

Carmine (E120), a natural red dye extracted from the dried females of the insect Dactylopius coccus var. Costa (eochineal), has been reported to cause hypersensitivity reactions. We report a case of occupational asthma and food allergy due to carmine in a worker not engaged in dye manufacturing. A 35-year-old nonatopic man, who had worked for 4 years in a spice warehouse, reported asthma and rhinoeonjunctivitis for 5 months, related to carmine handling in his work. Two weeks before the visit, he reported one similar episode after the ingestion of a red-colored sweet containing carmine. Peak flow showed drops higher than 25% related to carmine exposure. Prick tests with the cochineal insect and carmine were positive, but negative to common aeroallergens, several mites, foods, and spices. The methacholine test was positive. Specific bronchial challenge test with a cochineal extract was positive with a dual pattern (20% and 24% fall in FEV_i). Double-blind oral challenge with E120 was positive. The patient's sera contained specific IgE for various high-molecular-weight proteins from the cochineal extract, as shown by immunoblotting. Carmine proteins can induce IgE-mediated food allergy and occupational asthma in workers using products where its presence could be easily overlooked, as well as in dye manufacture workers.     

EpidemAAITO: Features of food allergy in Italian adults attending allergy clinics: a multi-centre study

Background Studies of the prevalence of different types of food allergy in adults are lacking.
Objective To define the prevalence of IgE-mediated food allergies in Italian adults attending allergy clinics and to assess possible differences associated with geographical position and/or dietary habits.
Methods Seventeen allergy outpatient clinics scattered throughout Italy participated to a multi-centre study in 2007. The number of atopic subjects and of food allergic patients along with clinical features were recorded by pre-defined criteria. Patients with unequivocal history of food allergy confirmed by positive skin prick test were included as cases.
Results Twenty five thousand six hundred and one subjects were screened; 12 739 (50%) were atopic, and 1079 (8,5%) had IgE-mediated food allergy. Sixty four percent of patients were females. Overall, the most frequent food allergy was the pollen–food allergy syndrome (55%), which was associated with oral allergy syndrome in 95% of cases and whose frequency decreased southbound. Forty-five percent of patients had a type 1 food allergy, in most cases (72%) caused by fruits and vegetables, and generally associated with a history of systemic symptoms. Type 1 food allergies represented 96% of food allergies in the South. Lipid transfer protein (LTP) accounted for 60% of sensitizations and caused most primary food allergies in all areas.
Conclusion Plant-derived foods cause most food allergies in Italian adults. The pollen–food allergy syndrome is the most frequent type of food allergy followed by allergy to LTP whose frequency increases southbound. The pattern of allergy to certain foods is clearly influenced by specific geographic features such as pollen exposure and dietary habits.     

Identification of IgE-binding epitopes on gliadins for patients with food allergy to wheat

BACKGROUND: Food allergy to wheat induces different symptoms as atopic eczema/dermatitis syndrome (AEDS), urticaria and more severe reactions as wheat-dependent exercise-induced anaphylaxis (WDEIA). Different gliadin classes are involved in this allergy but IgE-binding epitopes are known only on omega5-gliadins and for WDEIA cases. OBJECTIVES: The aim of the study was to identify IgE-binding epitopes on several gliadin classes and for several patients with different symptoms and ages. METHODS: Eleven sera were analysed by pepscan with overlapping synthetic peptides. RESULTS: Sera from five patients with anaphylaxis, urticaria or WDEIA, displayed strong IgE-binding to sequential epitopes of the repetitive domains of alphabeta, gamma, omega2 or omega5-gliadins with two immunodominant epitopes on omega5-gliadin and a consensus motif of the type QQX1PX2QQ (X1 being L, F, S or I and X2 Q, E or G). One patient allergic to deamidated wheat proteins also had IgE to a repetitive peptide of gamma and omega2-gliadins of the type QPQQPFP. Sera from four patients with AEDS detected no linear epitopes on gliadins, despite the fact that they contained specific IgE to alpha, beta, gamma or omega-gliadins. One child with AEDS recognized cysteine-containing sequences in the nonrepetitive domains of alphabeta and gamma-gliadins. CONCLUSION: B epitopes in wheat allergy were different from B epitopes of coeliac disease. Differences exist in IgE-binding epitopes between patients with food allergy to wheat. IgE from those suffering from WDEIA, anaphylaxis and urticaria detected sequential epitopes in the repetitive domain of gliadins whereas IgE from AEDS patients probably recognized conformational epitopes.     

IgE binding to soluble and insoluble wheat flour proteins in atopic and non-atopic patients suffering from gastrointestinal symptoms after wheat ingestion

BACKGROUND: The involvement of IgE-mediated hypersensitivity reactions in the genesis of gastrointestinal symptoms after ingestion of foods containing wheat has been rarely reported. OBJECTIVE: To detect IgE specifically binding to wheat proteins in the sera of atopic and non-atopic patients suffering from gastrointestinal symptoms after ingestion of wheat and to evaluate the reliability of skin prick test and CAP in the diagnosis of food allergy to wheat. METHODS: The sera of patients (10 atopic and 10 non-atopic) previously diagnosed as suffering from irritable bowel syndrome and complaining of symptoms after wheat ingestion were analysed by immunoblotting for IgE binding to water/salt-soluble and insoluble wheat flour proteins. RESULTS: All the atopic patients and only one of the non-atopic patients were positive to wheat CAP. For the patients tested, skin prick test was positive for all the atopic patients and for only one of the non-atopic patients. However, immunoblotting experiments showed the presence of specific IgE to wheat proteins in all the patients. Ten out of 11 of the wheat CAP-positive patients had IgE binding to a soluble 16-kDa band, but the same band was recognized, in a slighter way, by only two out of nine of the wheat CAP-negative patients. Moreover, although almost all of the patients were negative in CAP testing with gluten, 19 out of 20 recognized protein bands belonging to the prolamin fraction. CONCLUSIONS: For the atopic patients the positivity to skin prick test and CAP to wheat was in accordance with the immunoblotting results and a food allergy to wheat could be diagnosed. In these patients a major allergen was a 16-kDa band corresponding to members of the cereal alpha-amylase/trypsin inhibitors protein family, the major allergens involved in baker's asthma. In the non-atopic patients the positive immunoblotting results contrasted with the responses of the allergologic tests, indicating that the allergenic wheat protein preparations currently used are of limited value in detecting specific IgE to wheat and that the fraction of irritable bowel syndrome (IBS) patients with food allergy may be larger than believed.