PURPOSE: The aim of this study was to assess the clinical usefulness and added diagnostic value of specific IgE antibodies to wheat, gluten, and ω-5 gliadin in diagnosing wheat allergy and distinguishing wheat anaphylaxis. METHODS: This study included 196 children who visited Ajou University Hospital for suspicious food allergy. The subjects were divided into 2 groups: the wheat allergy (WA) and non-wheat allergy (non-WA) groups. Patients with wheat allergy were further divided into 2 subgroups according to their symptoms: the wheat allergy with anaphylaxis (WA(Ana)) and wheat allergy without anaphylaxis (WA(Non-Ana)) groups. Serum concentrations of total IgE and specific IgE antibodies to wheat, gluten and ω-5 gliadin were measured. RESULTS: The median values of specific IgE antibodies to wheat, gluten and ω-5 gliadin were significantly higher in the WA group than in the non-WA group, and the positive decision points (95% specificity) were at 3.12, 2.61, and 0.21 kUA/L, respectively. The combination of specific IgE antibodies to wheat and ω-5 gliadin resulted in the highest accuracy of 93.9% in diagnosing wheat allergy. In differentiating the WA(Ana) group from the WA(Non-Ana) group, only specific IgE antibody to ω-5 gliadin showed a significant difference at the optimal cutoff point of 1.56 kUA/L. CONCLUSION: Our results show that the individual levels of specific IgE antibodies to wheat, gluten or ω-5 gliadin may have a considerably high accuracy in diagnosing wheat allergy and that specific IgE antibody to ω-5 gliadin may be particularly useful in predicting wheat anaphylaxis.
Anaphylaxis ; Antibodies ; Child* ; Food Hypersensitivity ; Gliadin* ; Glutens* ; Humans ; Hypersensitivity ; Immunoglobulin E* ; Triticum* ; Wheat Hypersensitivity*

Wheat is a common cause of food allergy. Wheat-induced anaphylaxis (WIA) and wheat-dependent exercise induced anaphylaxis (WDEIA) are severe forms of immunoglobulin E (IgE) mediated allergic reaction to wheat protein. As the diagnosis of WIA or WDEIA is not easy because of the risk of oral challenge, identification of specific IgE of various wheat proteins is helpful for diagnosis. In Korea, there are only a few reports on WIA in adults. We report six cases of WIA diagnosed on the basis of clinical history and specific IgE of wheat proteins or provocation test. For immunologic evaluation of severe wheat allergy including WIA and WDEIA, it is important to measure specific IgE to each component of wheat including gluten and omega-5 gliadin not just measuring wheat-specific IgE.
Adult* ; Anaphylaxis* ; Diagnosis ; Food Hypersensitivity ; Gliadin ; Glutens ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Korea ; Triticum ; Wheat Hypersensitivity

PURPOSE: Component-resolved diagnostics (CRD) is expected to provide additional diagnostic information in allergic patients. PROTIA™ Allergy-Q 64 Atopy®, a recently developed CRD-based multiplex specific immunoglobulin E (sIgE) assay, can quantitatively measure sIgE to major allergen components. METHODS: The sIgE detection by PROTIA™ Allergy-Q 64 Atopy® and ImmunoCAP® assays was compared using the sera of 125 Korean allergic patients. Group 1 and 2 allergens of house dust mites (HDMs; Dermatophagoides farinae (Der f) 1 and Der f 2 in PROTIA™ Allergy-Q 64 Atopy®, Dermatophagoides pteronyssinus (Der p) 1 and Der p 2 in ImmunoCAP®), Bet v 1, Fel d 1, Que a 1, ω-5 gliadin, α-lactalbumin, β-lactoglobulin, casein and α-Gal were measured by both assays. RESULTS: Comparing the results from the 2 assays, the agreement rate for all the 10 allergens was > 88% (group 1 HDM allergen, 100%; group 2 HDM allergen, 94.6%; Bet v 1, 97.4%; Fel d 1, 90.5%; Que a 1, 89.2%; α-lactalbumin, 96%; β-lactoglobulin, 88%; casein, 88%; ω-5 gliadin, 96%; α-Gal, 100%). Correlation analysis indicated that, all the 10 allergen sIgEs showed more than moderate positive correlation (Pearson correlation coefficients > 0.640). Additionally, intra-class comparison showed more than high correlation for all the 10 allergens (Spearman's rank correlation coefficients > 0.743). CONCLUSIONS: PROTIA™ Allergy-Q 64 Atopy® is reliable and comparable to the ImmunoCAP® assay for component-resolved diagnosis.
Allergens ; Caseins ; Dermatophagoides farinae ; Dermatophagoides pteronyssinus ; Diagnosis ; Gliadin ; Humans ; Immunoassay ; Immunoglobulin E ; Immunoglobulins ; Pyroglyphidae

Wheat allergy is one of the commonest food allergies in childhood and it typically presents with IgE mediated reactions, including anaphylaxis. Seizures are not typically reported to be a direct manifestation of anaphylaxis, though it can occur secondary to hypoxia following significant haemodynamic compromise. We describe a case of a previously well infant, who presented with anaphylactic shock to wheat and responded well to the initial management, but subsequently developed a cluster of brief generalised tonic clonic seizures without any ongoing haemodynamic instability. The tryptase level that was performed at 4–5 hours post reaction was raised at 49.1 µg/L. Skin prick test to wheat, wheat specific IgE, the omega-5 gliadin IgE were positive. Extensive work-up was performed to look for an underlying cause of seizures and all returned negative. To our knowledge, this is the first case report describing an unusual presentation of multiple seizures in a young infant, in association with an anaphylactic episode. In the absence of any other seizure provoking factor and underlying cause, we believe the association is more likely causative than coincidental.
Anaphylaxis ; Anoxia ; Child ; Food Hypersensitivity ; Gliadin ; Humans ; Immunoglobulin E ; Infant ; Seizures ; Skin ; Triticum ; Tryptases ; Wheat Hypersensitivity

BACKGROUND/AIMS: The role of dietary factors in the pathogenesis of irritable bowel syndrome (IBS) is still unclear. The aim of this study was to compare IgG4 levels to common food antigens between patients with IBS and healthy controls. METHODS: Thirty-two patients diagnosed as IBS according to the Rome III criteria (12 diarrhea subgroup; 20 non-diarrhea subgroup) and 32 sex and age-matched healthy controls participated in the study. Serum IgG4 titers to 90 common foods were measured in each subject. The number of subjects with positivity defined as the cut-off value ≥ 0.7 U/mL was compared. RESULTS: Patients with IBS had significantly higher IgG4 titers to wheat, leek and taro compared to those of controls. Serum IgG4 titers to ginger, cocoa, walnut, white radish, onion, and lettuce in IBS patients tended to be higher than controls. IgG4 titers to wheat, gluten and gliadin in the diarrhea subgroup, and lettuce, leek and taro in the non-diarrhea subgroup tended to be higher compared with controls. The number of subjects with positivity to apple, orange, lettuce, and leek was significantly higher in IBS patients than controls. The number of subjects with positivity to apple, orange, gluten, and gliadin in the diarrhea subgroup, and egg white, pineapple, soybean, lettuce, and leek in the non-diarrhea subgroup was significantly higher compared with controls. CONCLUSIONS: Serum IgG4 antibody levels to some common foods are abnormally elevated in IBS patients. The type of foods with abnormally elevated serum IgG4 titers in the diarrhea subgroup may be different from that in the non-diarrhea subgroup.
Ananas ; Cacao ; Citrus sinensis ; Colocasia ; Diarrhea ; Egg White ; Ginger ; Gliadin ; Glutens ; Humans ; Immunoglobulin G* ; Irritable Bowel Syndrome* ; Juglans ; Lettuce ; Onions ; Raphanus ; Soybeans ; Triticum

Background: Wheat-dependent, exercise-induced anaphylaxis (WDEIA) is an allergic reaction induced by intense exercise combined with wheat ingestion. The gold standard for diagnosis of WDEIA is a food exercise challenge; however, this test is unacceptable for Chinese WDEIA patients and unable to be approved by the Ethics Committee of Chinese hospitals due to substantial risk. There are no diagnostic criteria for Chinese WDEIA patients. The aim of present study was to propose new practical diagnosis criteria for Chinese WDEIA patients. Methods: We prospectively included 283 clinically diagnosed WDEIA patients from January 1, 2010 to June 30, 2014, and in the meanwhile, three groups were enrolled which included 133 patients with the history of anaphylaxis induced by food other than wheat, 186 recurrent urticaria patients, and 94 healthy participants. Clinical comprehensive evaluation by allergists used as the reference gold standard, receiver operator characteristic (ROC) curves were plotted, areas under curve (AUC) for specific immunoglobin E (sIgE) were compared to evaluate the diagnostic value of IgE specific to wheat, gluten, and ω-5 gliadin. Patients were followed up by telephone questionnaire 1 year after diagnosis. Results: We reviewed 567 anaphylactic reactions in 283 WDEIA patients. Of these anaphylactic reactions, 415 (73.3%) reactions were potentially life-threatening anaphylaxis. Among the 567 anaphylactic reactions, 75% (425/567) occurred during exercise. The highest AUC (0.910) was observed for sIgE for gluten, followed by omega-5 gliadin (AUC 0.879). Combined gluten- and ω-5 gliadin-specific IgE testing provided sensitivity and specificity of 73.1% and 99.0%, respectively. During the 1-year follow-up period, repeat anaphylaxis was rare when patients observed strict avoidance of wheat products combined with exercise or other triggering agents. Conclusions In this study, we proposed diagnostic criteria and management of WDEIA patients in China. Our present study suggested that confirmed anaphylactic reactions triggered by wheat with positive sIgE to gluten and omega-5-gliadin may provide supportive evidence for clinicians to make WDEIA diagnosis without performing a food exercise challenge.
Adolescent ; Adult ; Allergens ; Anaphylaxis ; diagnosis ; China ; Exercise Test ; Female ; Gliadin ; analysis ; Humans ; Immunoglobulin E ; Male ; Middle Aged ; Prospective Studies ; Triticum ; Wheat Hypersensitivity ; diagnosis ; Young Adult

BACKGROUND/AIMS: Non-celiac gluten sensitivity has been increasingly recognized as a predisposing factor for irritable bowel syndrome (IBS)-like symptoms in Western populations where celiac disease (CD) is relatively common. In Asia where CD is rare, we wish to determine the prevalence of gluten protein associated serology in IBS patients, which has not been formally studied, and its relation to histological and human leukocyte antigen (HLA) markers. METHODS: We reviewed a consecutive cohort of Asian patients with IBS, who had undergone serologic testing for IgA against deamidated gliadin peptide antibodies (IgA DGP) and IgA anti-endomysium antibodies, and who also had duodenal biopsies during clinical workup. In addition, a subset of Chinese patients with positive serology was further tested for HLA-DQ2 and HLA-DQ8. RESULTS: Of 186 patients, 34 (18%) were positive for IgA DGP; bloating, abdominal pain, belching and diarrhea were the most commonly reported symptoms but diarrhea as the most bothersome symptom was significantly more common in IgA DGP positive patients. Mildly increased intra-epithelial lymphocytes on duodenal biopsy was also more common (29% vs. 9%, P = 0.001). Nine of 21 Chinese patients tested as IgA DGP positive undertook HLA-DQ2/DQ8 testing, with only 2 being positive for HLA-DQ8. All patients with positive IgA DGP reported symptom improvement with gluten withdrawal. CONCLUSIONS: We have described a series of Asian, mainly Chinese, patients with IBS who were tested positive for IgA DGP, and improved on a gluten exclusion diet. We believe this is the first report of non-celiac gluten sensitivity in Asia, a region where CD is uncommon.
Abdominal Pain ; Antibodies* ; Asia ; Asian Continental Ancestry Group* ; Biopsy ; Causality ; Celiac Disease ; Cohort Studies ; Diarrhea ; Diet ; Eructation ; Gliadin* ; Glutens ; Humans ; Immunoglobulin A ; Irritable Bowel Syndrome* ; Leukocytes ; Lymphocytes ; Prevalence* ; Serologic Tests

Specific IgE to gliadin was proposed as a marker for wheat dependent exercise induced anaphylaxis, while Tri a 14 was found to induce IgE response in baker's asthma. We evaluated whether these components could be used for discriminating phenotypes of wheat allergy. Twenty-nine patients who were wheat-induced anaphylaxis and/or urticaria (n=21, group I) and baker's asthma (n=8, group II) were enrolled. The prevalence of serum specific IgE to Tri a 14 was higher in group II (25%) than in group I (4.8%), while the serum specific IgE to gliadin was significantly higher in group I (70%) than in group II (12.5%). The cutoff value for predicting the baker's asthma using the ratio of serum specific IgE to Tri a 14 to gliadin was 742.8 optical densityx1,000/(kU/L) with high sensitivity and specificity. These findings suggest that Tri a 14/gliadin may be a potential marker for predicting baker's asthma.
Adult ; Anaphylaxis/immunology ; Antigens, Plant/*immunology ; Asthma/blood/diagnosis/immunology ; Biological Markers/blood ; Carrier Proteins/*immunology ; Female ; Gliadin/*immunology ; Humans ; Immunoglobulin E/*blood/immunology ; Male ; Phenotype ; Triticum/immunology ; Urticaria/immunology ; Wheat Hypersensitivity/*diagnosis/*immunology

BACKGROUND/AIMS: The aim of this study was to establish a pathogenetic mechanism of pancreatitis in celiac disease and IgG4-related disease using gluten-sensitive human leukocyte antigen (HLA)-DQ8 transgenic mice. METHODS: Transgenic mice expressing HLA-DQ8 genes were utilized. Control mice were not sensitized but were fed gliadin-free rice cereal. Experimental groups consisted of gliadin-sensitized and gliadin-challenged mice; nonsensitized mice with cerulein hyperstimulation; and gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation. RESULTS: Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation showed significant inflammatory cell infiltrates, fibrosis and acinar atrophy compared with the control mice and the other experimental groups. The immunohistochemical analysis showed greater IgG1-positive plasma cells in the inflammatory infiltrates of gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation compared with the control mice and the other experimental groups. Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation or gliadin-sensitized and gliadin-challenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs. CONCLUSIONS: Gliadin-sensitization and cerulein hyperstimulation of gluten-sensitive HLA-DQ8 transgenic mice resulted in pancreatitis and extrapancreatic inflammation. This animal model suggests that chronic gliadin ingestion in a susceptible individual with the HLA-DQ8 molecule may be associated with pancreatitis and extrapancreatic inflammation.
Animals ; Animals* ; Atrophy ; Autoimmune Diseases ; Bile Ducts ; Celiac Disease ; Ceruletide ; Eating ; Edible Grain ; Fibrosis ; Gliadin* ; Humans ; Inflammation* ; Kidney ; Leukocytes ; Lung ; Mice* ; Mice, Transgenic ; Models, Animal* ; Pancreatitis* ; Plasma Cells ; Salivary Glands

Wheat is the most widely cultivated grain and an important source of food and dietary protein. Wheat proteins are classified based on extraction in different solvents, which are albumin, globulin, prolamin (gliadin) and glutenin. The term 'gluten' contains approximately equal amounts of gliadin and glutenin and is the major determinant of the properties of wheat flour conferring cohesiveness and viscoelasticity that allows its dough to be processed into many kinds of food. Gluten is known to be responsible for triggering celiac disease and wheat allergy. Wheat allergy is primarily an IgE-mediated response. Clinical manifestations of wheat allergy are similar to those of other food allergies, with symptoms on the skin, gut and respiratory tract. Recent studies have shown that IgE to gliadin can be an indicator for risk of severe immediate reaction-like anaphylaxis and wheat-dependent, exercise-induced anaphylaxis (WDEIA). However, current in vitro test reagents for the diagnosis of wheat allergy mainly contain water-soluble wheat protein and a small amount of gluten, so there are some limitations to diagnose gluten allergy. Furthermore, there is no acceptable method to measure gluten in food products for preparing effective gluten-free diet. To overcome these limitations and to improve quality of life of wheat allergy sufferers, more work is needed. We report a case of a 4-year-old boy with gluten allergy who presented with urticaria after ingestion kneaded wheat flour with a brief review of the literature.
Anaphylaxis ; Celiac Disease ; Edible Grain ; Diet, Gluten-Free ; Dietary Proteins ; Eating ; Flour ; Food Hypersensitivity ; Gliadin ; Glutens ; Hypersensitivity ; Immunoglobulin E ; Indicators and Reagents ; Preschool Child ; Proteins ; Quality of Life ; Respiratory System ; Skin ; Solvents ; Triticum ; Urticaria ; Wheat Hypersensitivity