Takatsugu Komata

Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma

BACKGROUND NLR family, pyrin domain containing 3 (NLRP3), controls the activity of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of the procytokines IL-1beta and IL-18. Recent studies have shown associations of human NLRP3 polymorphisms with susceptibility to various inflammatory diseases; however, the association with allergic diseases remains unclear. OBJECTIVE We sought to examine whether NLRP3 polymorphisms are associated with susceptibility to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA). METHODS We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and conducted association analyses of NLRP3 using 574 and 1279 samples for food allergy and AIA, respectively. We further performed functional analyses of the susceptible SNPs. RESULTS Two NLRP3 SNPs (rs4612666 and rs10754558) were significantly associated with susceptibility to food-induced anaphylaxis (P = .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also showed a significant association (P = .000098). We could confirm the association with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P = .0096). Functional analysis revealed that the risk alleles of rs4612666 and rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA stability, respectively. CONCLUSION Our results indicate that the NLRP3 SNPs might play an important role in the development of food-induced anaphylaxis and AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will contribute to the development of novel diagnostic and therapeutic methods for food-induced anaphylaxis and AIA.

Measurement of Ara h 1‐, 2‐, and 3‐specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children

To cite this article: Ebisawa M, Movérare R, Sato S, Maruyama N, Borres MP, Komata T. Measurement of Ara h 1‐, 2‐, and 3‐specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children. Pediatr Allergy Immunol 2012: 23: 573–581.

Usefulness of Wheat and Soybean Specific IgE Antibody Titers for the Diagnosis of Food Allergy

BACKGROUND Since the first suggestion of threshold values for food specific IgE antibody levels in relation to clinical reactivity, several authors have proposed different threshold values for different allergens. We investigated the relationship between wheat/soybean specific IgE antibody levels and the outcome of wheat/soybean allergy diagnosis in children of different ages. METHODS A retrospective study was conducted in 536 children admitted consecutively to our clinic with the suspicion of wheat and/or soybean allergy. The children underwent an oral food challenge and blood samples for specific IgE measurement were obtained. RESULTS The children who reacted to the oral food challenge had higher specific IgE titers to the specific allergen compared to the non-reacting group. The risk for reaction increased 2.33-fold (95% CI 1.90-2.87) for wheat and 2.08-fold (95% CI 1.65-2.61) for soybean, with increasing levels of specific IgE. A significant difference between the ages of subjects pertained only to wheat. CONCLUSIONS We found a relationship between the probability of failed challenge and the concentration of IgE antibodies to both wheat and soybean. Age influences the relationship of allergen specific IgE levels to wheat and oral food challenge outcome. Younger children are more likely to react to low levels of specific IgE antibody concentration to wheat than older children.

Utility of the Peripheral Blood Basophil Histamine Release Test in the Diagnosis of Hen’s Egg, Cow’s Milk, and Wheat Allergy in Children

Background: The diagnosis of food allergy (FA) is made by oral food challenge tests (OFCs) that occasionally produce serious symptoms in patients; therefore, whether to perform OFCs should be carefully considered. The utility of the histamine release test (HRT) in the diagnosis of childhood FA has not been fully examined. Methods: Sixty-four subjects with suspected hen’s egg allergy, cow’s milk allergy (CMA), and wheat allergy (WA) were enrolled. The diagnosis of FA was made based on the outcomes of OFCs or a convincing history of symptoms after food ingestion within 6 months before or after sample collection. HRT was performed using an HRT Shionogi kit. The threshold of histamine release (HRT threshold), which was defined as the minimum concentration of food antigen to induce a 10% net histamine release, was analyzed in association with FA diagnosis. Results: Receiver operating characteristic analysis showed that the HRT threshold was useful in the diagnosis of heated egg allergy (HEA), raw egg allergy (REA), CMA, and WA. We were able to determine the cutoff value for the HRT threshold in relation to outcomes of OFCs. The cutoff value was 6 ng/ml of egg white antigen in HEA and REA (p < 0.01), 40 ng/ml of milk antigen in CMA (p < 0.01), and 500 ng/ml of wheat antigen in WA (p < 0.05). The efficiency was 70.3% for HEA, 78.0% for REA, 77.6% for CMA, and 70.7% for WA. Conclusions: We conclude that the HRT threshold measurement for egg white, milk, and wheat antigen is related to outcomes of OFCs and is useful in determining when OFCs should be performed.

The Skin Prick Test is Not Useful in the Diagnosis of the Immediate Type Food Allergy Tolerance Acquisition

BACKGROUND Some studies have been reported about positioning of SPT in the diagnosis of food allergy. On the other hand, it is not yet clear about the positioning of SPT in the diagnosis of tolerance acquisition of the immediate type food allergy. METHODS The retrospective study had been conducted for 236 egg allergic children (51.3 months in mean), 127 milk allergic children (53.4 months), and 96 wheat allergic children (42.6 months). The retrospective analysis of serum nonspecific and antigen-specific IgE levels, SPT, and OFC had been conducted for each allergic patient. All OFC had been conducted to verify the acquisition of tolerance against eliminated food. RESULTS The OFC was positive in 61 (25.8%) hens egg allergies, 34 (26.8%) milk allergies and 33 (34.4%) wheat allergies. The greatest AUC for each allergen is as following; hens egg for egg white specific IgE at 0.745, milk/histamine (wheal) index at 0.718, and wheat for wheal size at 0.597. For the predictive decision points, the highest accuracy rate was at 25.8% for an egg white wheal of 9.5mm, at 26.8% for a milk wheal of 9.5mm, and at 34.4% for a wheal of 6.5mm. CONCLUSIONS As a result of this analysis, the diagnostic accuracy of SPT had not been satisfactory to judge the acquisition of tolerance in allergic children for eggs, milk and wheat. Therefore, this is not a strong evidence to testify the tolerance of the immediate type food allergy.

Asthma diagnosis and treatment – 1005. Optimization for the withdrawal of inhaled corticosteroid treatment by monitoring fractional exhaled nitric oxide (feno) and lung functions

Results Subjects in recurrent asthma symptom group were 28 cases and those of non-recurrent asthma symptom group 27 cases (relapse rate: 50.9%). Any significant factors in background patients’ profiles, such as FeNO and pulmonary functions, were not associated with the recurrence of asthma. In recurrent asthma symptom group, FeNO was significantly increased by 3 months after withdrawal of ICS (from 31.8 ppb to 49.2 ppb). Among recurrent asthma symptom group, pulmonary functions were significantly decreased within 1 months (FVC: from 2.11L to 2.02L, FEV1.0: from 1.93L to 1.85L and %FEV1.0: from 98.1% of to 93.8%). Conclusions Although these factors at the time of ICS withdrawal could not predict asthmatic revival, it is highly recommended to follow asthmatic patients who quit ICS therapy by measuring pulmonary function and FeNO periodically.

Food allergy and anaphylaxis – 2054. Easy-to-use severity grading system for treatment of symptoms induced by oral food challenge

Methods From June 2008 to June 2012, the severity of SR was assessed at double-blind placebo-controlled food challenge test (DBPCFC) to evaluate if they were candidates for rush oral immunotherapy or not. The medical records of 342 patients who showed positive reaction at DBPCFC were analyzed. A hundred and forty-one were allergic to hen’s egg, 156 to milk and 45 to wheat. We modified the grading system proposed by Sampson HA in 2003 to enhance the convenience at clinical practice. It was proposed to indicate “severity of SR for each organ system, i.e., skin, mucosa, gastrointestinal tract, respiratory tract, cardiovascular, and neurological system. Systemic reactions for each organ were classified as Grade (G) 1 (mild), G2 (moderate), and G3 (severe). The severity score was based on the organ system mostly affected. We examined relationship between the severity score and its treatment during DBPCFC.

Food allergy and anaphylaxis – 2056. Clinical cross-reactivity of major food allergens among children

Methods We sought to clarify information of elimination diets related to clinical cross-reactivity of childhood major food allergens (hen’s egg, cow’s milk, wheat, soybean, and peanuts). We reviewed clinical records of patients who had visited to our department from January to December in 2010. One thousand eight hundreds twenty-two patients (1207 males and 615 females) were recruited to this study.

Food allergy and anaphylaxis – 2059. Mild symptoms induced by oral food challenge are not always associated with failed challenge results

Methods 4574 patients (average age 4.0 ± 2.6 years old, male-female ratio 1.89), who had received open-OFC to heated-egg or cow’s milk or wheat from 2005 to 2012, were enrolled to this study. Patients were divided into following 3 categories according to symptoms induced by OFC (primary diagnosis of FA). The “positive” group was patients who showed objective symptoms and “negative” group was patients who had not any symptoms. The third group was defined as “uncertain” who only showed subjective or weak objective symptoms such as slight erythema, mild abdominal pain or isolated cough. Patients with “negative” and “uncertain” group were asked to ingest causative foods or those products at home to confirm whether to induce any symptoms by the intake or not. In several weeks after OFC, we made the final diagnosis based on the information obtained from patients (final diagnosis of FA).

496 Cross Sectional Study of 1,822 Pediatric Food Allergy Patients.

Background The aim of this study is to clarify the cross section of pediatric food allergy patients. We investigated the profiles of food allergy (FA) patients seen in our department. Methods The number of food allergy patients seen in our department from January to December in 2010 was a total of 1,822 (male: 1207, female: 615, mean age: 5.8 ± 3.8 year). We collected and analyzed the clinical information of these patients from our medical record. We obtained information on the age of FA onset & FA diagnosis, clinical types of FA at the onset, causative food allergens, other allergic complications, and application of oral immunotherapy (OIT). Results The average age of FA onset was 8 months, and that of diagnosis was 1 year old, respectively. The most common clinical types of FA at the time of onset were infantile atopic dermatitis (AD) type with food allergy (66.4%) followed by immediate type (30.8%). Food allergens avoided by the patients were the total number of 4,203 items (2.1 items as average). The most common eliminated food was hens egg (1,245 cases; 29.6%), followed by cows milk (786 cases; 18.7%), peanut (449 cases; 10.7%), and wheat (407 cases; 9.7%). Food-dependent exercise-induced anaphylaxis (FDEIA) was the total of 18 cases, and the most common causative food for FDEIA was wheat (10 cases) followed by peach (4 cases). One hundred and seventy five cases (9.6%) were currently receiving OIT. Main causative foods under OIT were hens egg (63 cases), cows milk (80 cases), and wheat (30 cases). The average starting age of OIT was 7.1 years old. Regarding complications of allergic diseases other than FA, 1119 (61.4%) had atopic dermatitis, and 541 (29.7%) bronchial asthma. Conclusions We were able to clarify the cross section of food allergy patients in our department and to obtain the basic data to follow continuous transition of these patients.