Detection of Sensitization Profiles with Cellular In Vitro Tests in Wheat Allergy Dependent on Augmentation Factors (WALDA).

Wheat allergy dependent on augmentation factors (WALDA) is the most common gluten allergy in adults. IgE-mediated sensitizations are directed towards ω5-gliadin but also to other wheat allergens. The value of the different in vitro cellular tests, namely the basophil activation test (BAT) and the active (aBHRA) and passive basophil histamine-release assays (pBHRA), in the detection of sensitization profiles beyond ω5-gliadin has not been compared. Therefore, 13 patients with challenge-confirmed, ω5-gliadin-positive WALDA and 11 healthy controls were enrolled. Specific IgE (sIgE), skin prick tests, BATs, aBHRA, and pBHRA were performed with allergen test solutions derived from wheat and other cereals, and results were analyzed and compared. This study reveals a distinct and highly individual reactivity of ω5-gliadin-positive WALDA patients to a range of wheat allergens beyond ω5-gliadin in cellular in vitro tests and SPT. In the BAT, for all tested allergens (gluten, high-molecular-weight glutenin subunits, α-amylase/trypsin inhibitors (ATIs), alcohol-free wheat beer, hydrolyzed wheat proteins (HWPs), rye gluten and secalins), basophil activation in patients was significantly higher than in controls (p = 0.004-p < 0.001). Similarly, significant histamine release was detected in the aBHRA for all test substances, exceeding the cut-off of 10 ng/mL in all tested allergens in 50% of patients. The dependency of tests on sIgE levels against ω5-gliadin differed; in the pBHRA, histamine release to any test substances could only be detected in patients with sIgE against ω5-gliadin ≥ 7.7 kU/L, whereas aBHRA also showed high reactivity in less sensitized patients. In most patients, reactivity to HWPs, ATIs, and rye allergens was observed. Additionally, alcohol-free wheat beer was first described as a promising test substance in ω5-gliadin-positive WALDA. Thus, BAT and aBHRA are valuable tools for the identification of sensitization profiles in WALDA.

Two randomized crossover multicenter studies investigating gastrointestinal symptoms after bread consumption in individuals with noncoeliac wheat sensitivity: do wheat species and fermentation type matter?

BACKGROUND: Many individuals reduce their bread intake because they believe wheat causes their gastrointestinal (GI) symptoms. Different wheat species and processing methods may affect these responses. OBJECTIVES: We investigated the effects of 6 different bread types (prepared from 3 wheat species and 2 fermentation conditions) on GI symptoms in individuals with self-reported noncoeliac wheat sensitivity (NCWS). METHODS: Two parallel, randomized, double-blind, crossover, multicenter studies were conducted. NCWS individuals, in whom coeliac disease and wheat allergy were ruled out, received 5 slices of yeast fermented (YF) (study A, n = 20) or sourdough fermented (SF) (study B, n = 20) bread made of bread wheat, spelt, or emmer in a randomized order on 3 separate test days. Each test day was preceded by a run-in period of 3 d of a symptom-free diet and separated by a wash-out period of ≥7 d. GI symptoms were evaluated by change in symptom score (test day minus average of the 3-d run-in period) on a 0-100 mm visual analogue scale (ΔVAS), comparing medians using the Friedman test. Responders were defined as an increase in ΔVAS of ≥15 mm for overall GI symptoms, abdominal discomfort, abdominal pain, bloating, and/or flatulence. RESULTS: GI symptoms did not differ significantly between breads of different grains [YF bread wheat median ΔVAS 10.4 mm (IQR 0.0-17.8 mm), spelt 4.9 mm (-7.6 to 9.4 mm), emmer 11.0 mm (0.0-21.3 mm), P = 0.267; SF bread wheat 10.5 mm (-3.1 to 31.5 mm), spelt 11.3 mm (0.0-15.3 mm), emmer 4.0 mm (-2.9 to 9.3 mm), P = 0.144]. The number of responders was also comparable for both YF (6 to wheat, 5 to spelt, and 7 to emmer, P = 0.761) and SF breads (9 to wheat, 7 to spelt, and 8 to emmer, P = 0.761). CONCLUSIONS: The majority of NCWS individuals experienced some GI symptoms for ≥1 of the breads, but on a group level, no differences were found between different grains for either YF or SF breads. CLINICAL TRIAL REGISTRY: clinicaltrials.gov, NCT04084470 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04084470).

The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study.

BACKGROUND: Many individuals without coeliac disease or wheat allergy reduce their gluten intake because they believe that gluten causes their gastrointestinal symptoms. Symptoms could be affected by negative expectancy. Therefore, we aimed to investigate the effects of expectancy versus actual gluten intake on symptoms in people with non-coeliac gluten sensitivity (NCGS). METHODS: This randomised, double-blind, placebo-controlled, international, multicentre study was done at the University of Leeds (Leeds, UK), Maastricht University (Maastricht, the Netherlands), and Wageningen University and Research (Wageningen, the Netherlands). People aged 18-70 years with self-reported NCGS (ie, gastrointestinal symptoms within 8 h of gluten consumption) without coeliac disease and wheat allergy were recruited. Participants had to follow a gluten-free or gluten-restricted diet for at least 1 week before (and throughout) study participation and had to be asymptomatic or mildly symptomatic (overall gastrointestinal symptom score ≤30 mm on the Visual Analogue Scale [VAS]) while on the diet. Participants were randomly assigned (1:1:1:1; blocks of eight; stratified by site and gender) to one of four groups based on the expectation to consume gluten-containing (E+) or gluten-free (E-) oat bread for breakfast and lunch (two slices each) and actual intake of gluten-containing (G+) or gluten-free (G-) oat bread. Participants, investigators, and those assessing outcomes were masked to the actual gluten assignment, and participants were also masked to the expectancy part of the study. The primary outcome was overall gastrointestinal symptom score on the VAS, which was measured at and corrected for baseline (before breakfast) and hourly for 8 h, with lunch served after 4 h, and analysed per-protocol. Safety analysis included all participants incorporated in the per-protocol analysis. The study is registered at ClinicalTrials.gov, NCT05779358, and has ended. FINDINGS: Between Oct 19, 2018, and Feb 14, 2022, 165 people were screened and 84 were randomly assigned to E+G+ (n=21), E+G- (n=21), E-G+ (n=20), or E-G- (n=22). One person in the E+G+ group was excluded due to not following test day instructions, leaving 83 participants in the per-protocol analysis. Median age was 27·0 years (IQR 21·0-45·0), 71 (86%) of 83 people were women, and 12 (14%) were men. Mean overall gastrointestinal symptom score was significantly higher for E+G+ (16·6 mm [95% CI 13·1 to 20·0]) than for E-G+ (6·9 mm [3·5 to 10·4]; difference 9·6 mm [95% CI 3·0 to 16·2], p=0·0010) and E-G- (7·4 mm [4·2 to 10·7]; difference 9·1 mm [2·7 to 15·6], p=0·0016), but not for E+G- (11·7 mm [8·3 to 15·1]; difference 4·9 mm [-1·7 to 11·5], p=0·28). There was no difference between E+G- and E-G+ (difference 4·7 mm [-1·8 to 11·3], p=0·33), E+G- and E-G- (difference 4·2 mm [-2·2 to 10·7], p=0·47), and E-G+ and E-G- (difference -0·5 mm [-7·0 to 5·9], p=1·0). Adverse events were reported by two participants in the E+G- group (itching jaw [n=1]; feeling lightheaded and stomach rumbling [n=1]) and one participant in the E-G+ group (vomiting). INTERPRETATION: The combination of expectancy and actual gluten intake had the largest effect on gastrointestinal symptoms, reflecting a nocebo effect, although an additional effect of gluten cannot be ruled out. Our results necessitate further research into the possible involvement of the gut-brain interaction in NCGS. FUNDING: Government of the Netherlands Topsector Agri & Food Top Consortium for Knowledge and Innovation, AB Mauri Global Bakery Ingredients, Baking Industry Research Trust, Borgesius-Albert Heijn, CSM Innovation Centre, the International Maize and Wheat Improvement Center (CIMMYT), DSM Food Specialties, Fazer, Healthgrain Forum, the International Association for Cereal Science and Technology, the International Wheat Gluten Association, Lantmännen, Mondelez International, Nederlands Bakkerij Centrum, Nutrition & Santé, Puratos, Rademaker, Sonneveld Group, and Zeelandia HJ Doeleman.

Wheat gluten deamidation: structure, allergenicity and its application in hypoallergenic noodles.

BACKGROUND: Wheat gluten (WG) containing gliadin and glutenin are considered the main allergens in wheat allergy as a result of their glutamine-rich peptides. Deamidation is a viable and efficient approach for protein modifications converting glutamine into glutamic acid, which may have the potential for allergenicity reduction of WG. RESULTS: Deamidation by citric acid was performed to investigate the effects on structure, allergenicity and noodle textural properties of wheat gluten (WG). WG was heated at 100 °C in 1 m citric acid to yield deamidated WG with degrees of deamidation (DD) ranging from DWG-25 (25% DD) to DWG-70 (70% DD). Fourier-transform infrared and intrinsic fluorescence spectroscopy results suggested the unfolding of WG structure during deamidation, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed molecular weight shifts at the 35-63 kDa region, suggesting that the deamidation mainly occurred on low molecular weight glutenin subunits and γ- gliadin of the WG. An enzyme-linked immunosorbent assay of deamidated WG revealed a decrease in absorbance and immunoblotting indicated that the intensities of protein bands at 35-63 kDa decreased, which suggested that deamidation of WG might have caused a greater loss of epitopes than the generation of new epitopes caused by unfolding of WG, and thereby reduction of the immunodominant immunoglobulin E binding capacity, ultimately leading to the decrease in allergenicity. DWG-25 was used in the preparation of recombinant hypoallergenic noodles, and the hardness, elasticity, chewiness and gumminess were improved significantly by the addition of azodicarbonamide. CONCLUSION: The present shows the potential for deamidation of the WG products used in novel hypoallergenic food development. © 2023 Society of Chemical Industry.

Lactobacillus paracasei AH2 isolated from Chinese sourdough alleviated gluten-induced food allergy through modulating gut microbiota and promoting short-chain fatty acid accumulation in a BALB/c mouse model.

BACKGROUND: A large number of people worldwide suffer from gluten-induced food allergy. As investigated in our previous research, Lactobacillus paracasei AH2 isolated from traditionally homemade sourdough in Anhui province of China showed the potential to reduce the immune reactivity of wheat protein by in vitro evaluation. However, whether L. paracasei AH2 has a role in alleviating wheat allergy in an in vivo model and its underlying mechanisms have not been elucidated. RESULTS: In this study, the alleviative effects of L. paracasei AH2 on gluten-induced allergic response were evaluated. Compared with a gluten-allergic mouse, L. paracasei AH2 suppressed anaphylaxis symptoms, gluten-specific immunoglobulin E, histamine and interleukin-4. Moreover, L. paracasei AH2 attenuated splenomegaly and induced Th1 or Treg cell differentiation to modulate the Th1/Th2 immune balance toward Th1 polarization. Short-chain fatty acid (SCFA) levels were enhanced after L. paracasei AH2 supplementation, contributing to allergy relief as well as reducing the pH of colonic contents. The α and ß diversities of the gut microbiota were modulated by L. paracasei AH2 with increased relative abundance of Lacticaseibacillus and SCFA producers (Faecalibaculum, Alloprevotella and Bacteroides genera), as well as decreased unfavorable Lachnospiraceae_NK4A136_group and Alistipes. Additionally, L. paracasei AH2 protected the intestinal barrier function by upregulating tight junctions and improved the antioxidant activities in serum. CONCLUSION: Our findings indicate that L. paracasei AH2 could act as a potential probiotic for relieving wheat allergy by modulating the gut microbiota and elevating SCFA levels. © 2023 Society of Chemical Industry.

[AN ADOLESCENT CASE OF HAE-NL-C1INH (WHO WAS) MISDIAGNOSED WITH WHEAT ALLERGY AND MULTIPLE DRUG ALLERGIES].

Hereditary angioedema (HAE) is frequently misdiagnosed as drug allergy. It is essential to differentiate HAE from allergy. Diagnosing HAE-normal-C1INH (conventional HAE type III), presenting normal C1-INH, is even more difficult. Here, we report a case of a 17-year-old female diagnosed with HAE and having labeled wheat and multiple drug allergies. She had been suffering from skin edema and abdominal symptoms since childhood. After taking wheat at 13 years old, she had multiple episodes of the same symptoms. Wheat allergy was suspected, and she started eliminating wheat. Multiple attacks were observed after several drug use, and drug allergy was labeled. However, her attacks did not improve after eliminating wheat and the suspected drugs. Her C4 and C1-INH activity was normal, but we diagnosed her with HAE-normal-C1INH based on her family history, multiple attacks after dental procedures, ineffective antihistamines, and significant efficacy of C1-INH infusion. A double-blind, placebo-controlled wheat challenge test at our hospital was negative, and wheat removal was lifted. Drugs could be de-labeled by allergic tests and history. Repeated attacks of unexplained edema and abdominal pain should be differentiated from HAE and lead to an appropriate diagnosis.

Wheat-dependent exercise-induced anaphylaxis: subtypes, diagnosis, and management.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is an IgE-mediated food allergy with allergic symptoms ranging from intermittent urticaria to severe anaphylaxis that occurs when wheat ingestion is combined with augmenting cofactors such as exercise, non-steroidal anti-inflammatory drugs, or alcohol. In most cases, patients are identified by sensitization to ω5-gliadins in the gluten fraction of wheat. ω5-gliadin-negative subtypes of WDEIA are often difficult to diagnose and may be caused by Tri a 14 (wheat lipid transfer protein), after percutaneous sensitization with hydrolyzed wheat proteins, or, in rare cases, by cross-reactivity to grass pollen. Diagnosis is established based on the patients' history in combination with serum IgE profile, skin testing, basophil activation tests, and challenge tests with cofactors. Individual dietary counselling remains the central pillar in the management of WDEIA patients. A completely wheat-free diet is a possible option. However, this appears to promote tolerance less than continued regular consumption of gluten-containing cereals in the absence of cofactors. All patients should have an emergency set for self-treatment including an adrenaline autoinjector and receive adequate instruction. More data are needed on sublingual immunotherapy for WDEIA, a potentially promising therapeutic prospect. This article provides an overview of current knowledge on the diagnosis and management of WDEIA including an optimized challenge protocol using wheat gluten and cofactors.

Alpha/Beta Gliadin MM1 Is a Novel Antigen for Wheat-Dependent Exercise-Induced Anaphylaxis.

INTRODUCTION: Screening for ω-5 gliadin specific IgE antibody (sIgE) has high diagnostic utility in cases of suspected wheat-dependent exercise-induced anaphylaxis (WDEIA); however, negative cases may require confirmatory tests, such as the oral challenge test. Thus, newly identified allergens that can be used for the serological diagnosis of WDEIA are needed. This study aimed to identify additional sIgE biomarkers of WDEIA. METHODS: Forty-two patients with WDEIA (5 negative/37 positive for ω-5 gliadin sIgE) were enrolled. For comparison, 8 patients with immediate-type wheat allergy without WDEIA and 20 healthy controls without wheat allergy were also enrolled. Extracted wheat proteins were separated by 2D-PAGE. Proteins that reacted with serum IgE antibody in 2D Western blotting (2D-WB) were identified using mass spectrometry. Recombinant proteins were synthesized in Escherichia coli, and the antigenicity was tested using ELISA and the basophil activation test. RESULTS: In 2D-WB, nine proteins reacted with the serum IgE antibody from at least 60% of patients with WDEIA (n ≥ 25/42). ELISA revealed that alpha/beta gliadin MM1 exhibited the highest positive immunoreactivity in 23 of 26 patients who were positive for ω-5 gliadin sIgE (88%) and in 5 of 5 patients who were negative for ω-5 gliadin sIgE (100%). Alpha/beta gliadin MM1 exhibited significantly higher basophil activation in 14 patients with WDEIA when compared to 5 individuals without a wheat allergy. CONCLUSIONS: Alpha/beta gliadin MM1 sIgE exhibited the highest seropositivity, even among patients who were negative for ω-5 gliadin sIgE. The inclusion of alpha/beta gliadin MM1 in allergen-sIgE tests may improve the sensitivity for diagnosing WDEIA.

Challenge-confirmed diagnosis restores quality of life in cofactor-dependent wheat allergy.

BACKGROUND: Food allergies including cofactor-dependent allergies such as cofactor-dependent wheat allergy (CDWA) decrease the quality of life (QOL) of patients. OBJECTIVE: To define the health-related QOL and fears in patients with CDWA and to evaluate the impact of diagnosis confirmation by oral challenge test (OCT). METHODS: Patients with CDWA diagnosed by clinical history, sensitization, and OCT were invited to participate. Clinical characteristics, patients' fears, self-perceived overall QOL, the Food Allergy Quality of Life Questionnaire-Adult Form score, and the risks and benefits of OCT were evaluated after the final diagnosis. RESULTS: A total of 22 adults with CDWA (13 male, 9 female; mean age 53.5 years; median 5 years until diagnosis) were included. Specific immunoglobulin E (IgE) levels for gluten proteins were inversely correlated with the reaction threshold (P < .05). Higher reaction severity in the patients' histories correlated with increased basal serum tryptase levels (P = .003) and gluten and gliadin specific IgE (P < .05), but not to QOL. After the first allergic reaction, patients reported a drop in QOL (P < .001). Challenge-confirmed diagnosis and medical consultation could restore the patients' QOL (P < .05) and reduce their fear of further reactions (P < .01). No severe reactions occurred during OCT, which was rated as not stressful and highly beneficial. Compared with patients with CDWA diagnosed without OCT in the literature, health-related QOL was less impaired (mean Food Allergy Quality of Life Questionnaire-Adult Form score 3.8), especially regarding the emotional impact (P < .001 vs existing literature). CONCLUSION: Until final diagnosis, patients with CDWA have a severe physical and psychological burden. OCT is a safe method to confirm the diagnosis, restore the patients' severely affected QOL, and reduce their fear of further reactions.

Allergenicity of wheat protein in diet: Mechanisms, modifications and challenges.

Wheat is widely available in people's daily diets. However, some people are currently experiencing IgE-mediated allergic reactions to wheat-based foods, which seriously impact their quality of life. Thus, it is imperative to provide comprehensive knowledge and effective methods to reduce the risk of wheat allergy (WA) in food. In the present review, recent advances in WA symptoms, the major allergens, detection methods, opportunities and challenges in establishing animal models of WA are summarized and discussed. Furthermore, an updated overview of the different modification methods that are currently being applied to wheat-based foods is provided. This study concludes that future approaches to food allergen detection will focus on combining multiple tools to rapidly and accurately quantify individual allergens in complex food matrices. Besides, biological modification has many advantages over physical or chemical modification methods in the development of hypoallergenic wheat products, such as enzymatic hydrolysis and fermentation. It is worth noting that using biotechnology to edit wheat allergen genes to produce allergen-free food may be a promising method in the future which could improve the safety of wheat foods and the health of allergy sufferers.

A Meta-Analysis of the Prevalence of Wheat Allergy Worldwide.

Wheat allergy is a primary disease of food allergy, and its global prevalence is unclear. This study aimed to characterize the latest worldwide prevalence of wheat allergy based on five different diagnostic methods. Study searches were conducted in Web of Science, PubMed, Ovid LWW, and Cochrane database, with a time limit of 1 January 2007 to 1 September 2022. The review and screening of the articles was undertaken by two independent reviewers. The statistical analysis was conducted by R. A total of 56 articles were finally included. The prevalence of wheat allergy was 0.63% (95% CI: 0.43-0.87%) for self-reported, 0.70% (95% CI: 0.18-1.22%) for self-reported physician-diagnosed, 0.22% (95%CI: 0.07-0.65%) for skin prick test positive, 0.97% (95% CI: 0.43-2.20%) for specific immunoglobulin E positive, and 0.04% (95% CI: 0-0.16%) for food challenge. However, food challenge can be largely subjective, and the results were only based two countries, so the prevalence of wheat allergy confirmed by food challenge may be not entirely trustworthy. In conclusion, investigating the prevalence of wheat allergy in the real world as accurately as possible will contribute to the prevention, management, and risk assessment of wheat allergy.

Evaluation of gut microbiota of iranian patients with celiac disease, non-celiac wheat sensitivity, and irritable bowel syndrome: are there any similarities?

BACKGROUND AND AIMS: Individuals with celiac disease (CD), non-celiac wheat sensitivity (NCWS), and irritable bowel syndrome (IBS), show overlapping clinical symptoms and experience gut dysbiosis. A limited number of studies so far compared the gut microbiota among these intestinal conditions. This study aimed to investigate the similarities in the gut microbiota among patients with CD, NCWS, and IBS in comparison to healthy controls (HC). MATERIALS AND METHODS: In this prospective study, in total 72 adult subjects, including CD (n = 15), NCWS (n = 12), IBS (n = 30), and HC (n = 15) were recruited. Fecal samples were collected from each individual. A quantitative real-time PCR (qPCR) test using 16S ribosomal RNA was conducted on stool samples to assess the relative abundance of Firmicutes, Bacteroidetes, Bifidobacterium spp., and Lactobacillus spp. RESULTS: In all groups, Firmicutes and Lactobacillus spp. had the highest and lowest relative abundance respectively. The phylum Firmicutes had a higher relative abundance in CD patients than other groups. On the other hand, the phylum Bacteroidetes had the highest relative abundance among healthy subjects but the lowest in patients with NCWS. The relative abundance of Bifidobacterium spp. was lower in subjects with CD (P = 0.035) and IBS (P = 0.001) compared to the HCs. Also, the alteration of Firmicutes to Bacteroidetes ratio (F/B ratio) was statistically significant in NCWS and CD patients compared to the HCs (P = 0.05). CONCLUSION: The principal coordinate analysis (PCoA), as a powerful multivariate analysis, suggested that the investigated gut microbial profile of patients with IBS and NCWS share more similarities to the HCs. In contrast, patients with CD had the most dissimilarity compared to the other groups in the context of the studied gut microbiota.

Efficacy and safety of omalizumab in adult patients with wheat-dependent exercise-induced anaphylaxis: Reduction of in vitro basophil activation and allergic reaction to wheat.

BACKGROUND: In patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), anaphylactic shock occurs frequently, therefore avoidance of wheat products is recommended. We aimed to evaluate efficacy and safety of long-term omalizumab treatment for adult patients with WDEIA. METHODS: In this phase 2, multicentre single-arm trial, 20 adult patients with WDEIA were enrolled (UMIN 000019250). All patients were administered 150-600 mg of omalizumab subcutaneously and evaluations (basophil activation and blood examination) were performed at regular intervals during administration period (0-48 weeks) and observation period (48-68 weeks). Primary endpoint was proportion of the patients who achieved a basophil activation rate below 10% with fractionated wheat preparations, and secondary endpoint was proportion of the patients with no allergic reactions after wheat products ingestion. RESULTS: During the omalizumab treatment, more than 80% of the patients achieved the basophil activation rate less than 10% against all fractionated wheat preparations, and 68.8% of the patients who achieved the primary endpoint experienced no allergic reaction. During the observation period, the proportion of the patients who achieved a basophil activation rate below 10% decreased gradually, and the proportion of patients with positive allergic reactions increased gradually thereafter and reached maximum of 46.7%. Severe adverse events were not observed during the study. CONCLUSIONS: Long-term omalizumab treatment is safe and effective for adult patients with WDEIA when assessed by basophil activation rate with wheat allergens as well as allergic reactions after lifting of restrictions on wheat intake. However, this is not enough to achieve desensitization.

A potential role of gliadin extract skin prick test in IgE-mediated wheat allergy.

BACKGROUND: Wheat extracts containing both water/salt and alcohol soluble proteins may increase extract's accuracy for diagnosing IgE-mediated wheat allergy. OBJECTIVE: This study aimed to determine the performance of new invented in-house prepared wheat extracts for skin prick test (SPT). METHODS: Children aged 1-18 years with history of immediate wheat allergy were recruited. Four in-house prepared wheat extracts (wheat-Coca-10%EtOH, and 3 new invented extracts, wheat-salt, gliadin, and glutenin) and a commercial wheat extract were used for SPT. Serum specific IgE (sIgE) to wheat and omega-5 (ω-5) gliadin were also determined. Oral food challenge (OFC) with wheat flours was performed in all patients except those with history of wheat-induced anaphylaxis or with recent symptoms within the past 6 months. RESULTS: Thirty-one children were recruited. Of those, 14 were excluded from OFC (12 with history of anaphylaxis and 2 with recent symptom). OFC was positive in 8 of 17 children. Of the 5 extracts and sIgE to wheat and ω-5 gliadin, gliadin extract provided the best SPT performance with 84.2% sensitivity, 88.9% specificity, 94.1% positive predictive value (PPV), 72.7% negative predictive value (NPV), 7.59 positive likelihood ratio (LR), 0.18 negative LR, and 85.7% accuracy. CONCLUSIONS: Compared to other in-house and commercial wheat extracts and sIgE to wheat and ω-5 gliadin, SPT with an in-house gliadin extract yielded the highest performance for the diagnosis IgE-mediated wheat allergy.

Anemia in non-celiac wheat sensitivity: Prevalence and associated clinical and laboratory features.

BACKGROUND: Patients suffering from non-celiac wheat sensitivity (NCWS) frequently report extra-intestinal symptoms, such as anemia. AIMS: We investigated the prevalence and associated clinical features of anemia in NCWS patients. METHODS: Data from 244 NCWS patients, diagnosed by double-blind placebo-controlled wheat challenge, were retrospectively reviewed and compared with 2 control groups (celiac disease (CD) and irritable bowel syndrome (IBS)). Furthermore, 31 NCWS anemic patients were prospectively re-evaluated after at least 12 months on the "strict" wheat-free diet (WFD). RESULTS: Anemia prevalence in NCWS patients was 34.8% (mean hemoglobin 10.4 ± 1.4 g/dl), significantly higher than in IBS (17.4%, P = 0.03), but not in CD ones. The NCWS group, on the whole, had sideropenic-like features with low serum iron and altered iron deposits. Both anemia prevalence and sideropenic-like features were more evident in CD than in NCWS patients, whereas only a few IBS subjects showed such features. Significant differences were found in anemic vs non-anemic NCWS patients as regards to female sex, diagnostic delay, poly/hypermenorrhea, iron deficiency, and higher TSH values. A long-term WFD significantly reduced anemia and improved iron metabolism. CONCLUSION: Microcytic/hypochromic anemia and altered iron metabolism occur frequently in NCWS and can be treated with a long-term strict WFD. NCWS should be included in differential diagnosis of anemic patients with "functional gastrointestinal troubles".

Clinical cross-reactivity of wheat and barley in children with wheat allergy.

BACKGROUND: Several studies have reported in vitro cross-reactivity between wheat and barley. However, evidence regarding the clinical cross-reactivity of wheat and barley is limited. This study examined the clinical cross-reactivity of barley and wheat among children with immediate-type wheat allergies. METHODS: We examined the threshold dose of a wheat oral food challenge for wheat-allergic children. We examined the reactivity of barley, and the oral food challenges of barley tea and barley rice were implemented as needed. We measured the specific immunoglobulin E (sIgE) levels in wheat, ω-5 gliadin, and barley. RESULTS: We evaluated 53 children (39 [74%] boys) with a median age of 6.6 years. Among them, 39 (74%) patients had a history of anaphylaxis to wheat. The median wheat-, barley-, and ω-5 gliadin-sIgE levels were 57.3, 12.1, and 3.2 kUA /L, respectively. Twelve patients reacted to barley tea (1.8 mg), 14 reacted to barley rice (220-440 mg), and 27 were tolerant to barley tea and barley rice. Barley-allergic patients had significantly higher wheat- and ω-5 gliadin- and barley-sIgE levels and significantly lower threshold doses of wheat than barley-tolerant patients. Omega-5 gliadin-sIgE was the most useful predictor of barley allergy among wheat-allergic patients; the ω-5 gliadin-sIgE 95% positive predictive value for barley allergy was 4.6 kUA /L. CONCLUSIONS: Half of wheat-allergic children reacted to barley. A lower threshold dose of wheat is related to cross-reactive barley allergies. Omega-5 gliadin-sIgE predicts cross-reactive barley allergy in children allergic to wheat. Clinical cross-reactivity to barley should be considered in the management of wheat-allergic children.