Specific IgE Titers Research Articles

Inhibition of TLR4 and NLRP3 leads to the exacerbation of IgE specific antibodies in mouse allergic models based on subcutaneous or intranasal immunization respectively

A significant increase in the prevalence of diseases linked with IgE production can be seen in recent years, but the question about the role of TLR receptors in this process remains controversial. According to the hygiene hypothesis, the decrease of the contact of the individual with pathogens that contain PRR receptor ligands in the recent years leads to the development of allergic diseases. The aim of this work was to investigate whether TLR4 and NLRP3 receptor activation contributes to allergen-specific antibody formation. BALB/c mice were immunized according to two different protocols. In the first one, OVA antigen was administered in 0.1 µg dose 2-3 times a week for 6 weeks by subcutaneous route. In the second one, OVA was administered in 0.3 µg dose intranasally in combination with 4 ng of benzo(a)pyrene (BaP) 2 times a week for 8 weeks. In both cases, TLR4 and NLRP3 receptor inhibitors, namely TLR4-IN-C34 in 1 mg/kg dose and CY- 09 in 20 mg/kg dose respectively were also administered to the some of the mice. Specific antibody production was determined by ELISA. Immunization of mice with TLR4-IN-C34 significantly (p 0.01) amplify IgE production (about 2.5 times in comparison with control group), but has no effect on specific IgG1 production in subcutaneous model. Specific IgE titers in the control group immunized without small molecule inhibitor and in the TLR4-IN-C34 group were (3±0.6) × 103 and (8±2) × 103, respectively. In this model, CY-09 administration has no effect on humoral immune response. In the secondary (intranasal) model, BaP significantly increase specific IgE and IgG1 production. CY-09 but not TLR4-IN-C34 administered in combination with BaP significant (p 0.05) and approximately 2 times enhances specific IgE but not IgG1 production. Specific IgE titers in the control group without inhibitor and in the CY-09 group were (2.0±0.4) × 102 and (5.1±0.3) × 102, respectively. So, PRR-activation, in our case activation of TLR4 in the model based on subcutaneous immunization or NLRP3 in the model based on intranasal antigen administration with BaP suppressed the production of allergen-specific IgE, but not IgG1. These data are in consistent with the hygiene theory of allergy development.

The spectrum of pollen sensitization in children with allergic diseases living in the Rostov region

Objective: to investigate the characteristics of pollen sensitization in children with established diagnoses of bronchial asthma (BA) and atopic dermatitis (AD) living in the Rostov region. Materials and methods: patients suffering from BA (n = 53), they made up the first group and patients with AD (n = 65), the second group were examined. All children underwent a comprehensive clinical and laboratory examination. Immunochemiluminescent assay by the Immulight 2000XPi analyzer was used to determine specific IgE. Results: the analysis of the obtained results showed that sensitization to tree pollen was quite often noted - at least a quarter of those examined with BA and about 20% of children with AD had elevated titers of specific IgE to these allergens. The study of the level of specific IgE to meadow grass pollen showed that in the first group an allergic reaction to pollen of bent grass (31.5%), bonfire (33.3%), timothy grass (29.6%) and fescue (28.3%) was noted more often. In the second group, elevated levels of specific IgE were registered in relation to grasses such as bent grass (31.80%), bonfire (27.7%) and timothy grass (21.5%). The highest level of sensitization in patients with respiratory manifestations of allergy was registered in relation to weed pollen: ragweed (40.7%), quinoa (22.2%) and chamomile (14.8%). Conclusion: this study made it possible to identify allergens that play the most important role in the pathogenesis of BA and AD in children living in the Rostov region.

Single Nucleotide Polymorphism of Dectin-1 Gene Associates with Atopic Dermatitis in Children

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with complex and multifactorial pathophysiology, involving elements of barrier dysfunction, alterations in cell-mediated immune responses, IgE sensitization, and environmental factors. This encourages the search for predictors of disease development among both genetic markers and environment. AIM: The aim of the study was to examine if genetic factors of Malassezia recognition, or Malassezia colonization may be related to IgE sensitization or to severity of AD. METHODS: The study included 106 patients with eczema and 103 healthy children. Specific IgE against Malassezia mix (m227) was analyzed in 51 patients using immunochemiluminescent method on the ImmunoCAP 100 (Thermo Fisher Scientific Inc., Phadia, Sweden). Genotyping for rs7309123 in Dectin-1 was performed using Real-time PCR. The level of colonization by Malassezia in the scale samples was determined by a real-time PCR assay. RESULTS: Increased IgE to Malassezia spp. was observed in 29,4% of children with eczema. Higher Malassezia spp. – specific IgE titer positively correlated with severity of AD, age of onset, head–neck type of AD, and a higher total IgE. GG genotype rs7309123 Dectin-1 is significantly more often found in the patients than in the control group, but no correlation with IgE sensitization to Malassezia was found. Malassezia restricta and M. globosa were predominant in patients and controls, with some predominance of M. globosa over M. restricta among patients. CONCLUSION: Sensitization to Malassezia, genetic markers in Dectin-1, and Malassezia colonization of the skin can be tools for studying the gene-environment interactions in the pathogenesis of AD.

Atopic Status in Children with Asthma and Respiratory Allergies—Comparative Analysis of Total IgE, ImmunoCAP Phadiatop/fx5 and Euroimmun Pediatric Immunoblot

Introduction: An atopic status assessment (skin prick test or specific immunoglobulin (sIgE)) in asthmatic children is considered a milestone in identifying potential risk factors and triggers provoking loss of asthma control and asthma exacerbation. Objective: The study aims to perform a comparative analysis of different laboratory methods for a serological assessment of an atopic status in asthma and respiratory allergies in children. Material and methods: A total of 86 children were included, all of whom were diagnosed with bronchial asthma, aged from 5 to 17 years and screened for total IgE level using enzyme-linked immunosorbent assay (ELISA). In 48 randomly selected children, we performed a semi-quantitative serological in vitro assessment of the specific IgE antibodies against food and aeroallergen, using two different laboratory methods—Euroimmun Immunoblot and ImmunoCAP (Phadiatop/fx5). Results: In 70% of the children with a history of allergies, and 65.3% without clinically manifested allergies, multiscreen test ImmunoCAP Phadiatop/fx5 showed positivity and confirmed atopy. Our results showed a significant moderate to strong correlation between multiscreen ImmunoCAP Phadiatop/fx5, and Euroimmun specific IgE titers against aero-allergens—cats, mites, tree mix and food allergens—soy, wheat (р = 0.006), rice, р = 0.090), apple р = 0.007) and peanut. A sensitivity of 63% and specificity of 73.5% was observed for EUROIMMUN Pediatric (food allergens, IgE titer > 1) compared with the gold standard ImmunoCap/fx5. The mean value of total IgE is significantly higher in children with asthma and concomitant with allergic rhinitis compared to those without allergic rhinitis (mean 202.52 U/mL, IQR 102.50 (24.20–363.95) vs. 316.68, IQR 261.00 (109.20–552.50), p = 0.005). Conclusion: Establishing the spectrum of the most common respiratory and food allergens is an essential factor for maintaining asthma control, both through a strategy to avoid allergen exposure and by developing a recommendation plan. The immunoblotting technique is easily applicable in daily clinical and laboratory practice. It is also a cost-effective and reliable alternative to the “gold standard” ImmunoCAP Phadiatop/fx5 in diagnosing atopy in children.

The Majority of Children Sensitized Before School-Age Develop Allergic Disease Before Adulthood: A Longitudinal Population-Based Study

Allergic sensitization increases the risk of asthma and allergic rhinitis, but the impact of age at onset of sensitization is less studied. To examine the cumulative incidence of asthma and rhinitis up to age 19 years in relation to age at onset of sensitization to airborne allergens. All children in grade 1 and 2 (median age, 8 years) in 2 municipalities in Northern Sweden were invited to undergo skin prick tests and answer a questionnaire about allergic diseases, and 88% participated. At ages 12 and 19 years, the protocol was repeated, and 1510 individuals participated in all 3 examinations. Specific IgE data were collected in a random sample at age 19 years (n= 770). Onset of sensitization was defined: 8 years or less, 8 to 12 years, 12 to 19 years, and never sensitized. Adjusted Poisson regression was used to calculate risk ratios (RRs). At 19 years, those sensitized at 8 years of age or earlier had the highest risk of asthma (RR, 4.68; 95% CI, 3.15-6.97) and rhinitis (RR, 22.3; 95% CI, 13.3-37.6), and 84% had developed either asthma or rhinitis. The combination of sensitization at age 8 years or earlier and family history of allergic diseases rendered high risks for asthma (RR, 10.6; 95% CI, 6.71-16.7) and rhinitis (RR, 36.3; 95% CI, 18.9-69.7). Individuals sensitized at age 8 years or earlier showed significantly highest level of sensitization, as judged by number of positive skin test results and titers of specific IgE. Most individuals with sensitization at age 8 years or earlier developed asthma or rhinitis before young adulthood. The high level of sensitization in those sensitized early contributes to the high incidence of allergic airway conditions.

Suitable Interpretation of Skin Prick Test and Biomedical Guidance Leads to a Better Clinical State in Atopic Individuals with High Indoor Permanence: Possible Therapeutic Implications

Indoor conditions contribute to allergen sensitization and multiple allergens reactivity, mainly for inhaled allergens. This study analyzes if Skin Prick Test (SPT) combined with efficient individual biomedical guidance about allergy development’s social, biological, and environmental aspects can yield a better clinical state with therapeutic implications for atopic individuals with high indoor permanence. We recruited atopic and non-atopic volunteers (clinically and in vitro diagnosed) with indoor permanence above 15 h per day and without previous SPT evaluation. The SPT and serum anti-allergen IgE analyses were performed individually in person, demonstrated, and discussed by the practitioners. Six months after, SPT and specific IgE titers determination were repeated, and a questionnaire to evaluate the effectiveness of the practitioner’s orientation was performed. After six months, 14% of atopic volunteers reported changes in their social habits, 30% said that they avoid the development of allergies clinical symptoms, and 68% reported a substantial improvement in their health after being informed mentored about their allergen reactivity. The control non-atopic group, as expected, reported no changes in social habits, the maintenance of total avoidance of allergic symptoms, and almost no improvement of their health. Reduced SPT and serum allergen-specific IgE titers were detected in the atopic individuals corroborating with questionnaire results. Our results indicated that SPT, followed by an individual and efficient discussion about the main biomedical aspects of allergy development, could exert a pronounced therapeutic role in allergy development by high indoor permanence individuals.

Moulds and Staphylococcus aureus enterotoxins are relevant allergens to affect Type 2 inflammation and clinical outcomes in chronic rhinosinusitis patients.

BackgroundSensitisation to moulds and Staphylococcus aureus enterotoxins (SEs) is associated with the pathophysiology of both asthma and chronic rhinosinusitis (CRS). The purpose of this study was to clarify the contribution of sensitisation to these allergens to Type 2 inflammation in the blood, nose and the lower airways, and clinical outcomes in CRS patients.MethodsWe prospectively enrolled 56 CRS patients who underwent endoscopic sinus surgery (ESS) (20 with comorbid asthma) and 28 healthy controls between October 2015 and December 2017. CRS patients were followed up for 12 months after surgery. Type 2 inflammation-related biomarkers were analysed using blood, resected tissue samples and sputum. 10 allergens including Alternaria, Aspergillus and SEs were measured. Type 2 inflammation-related biomarkers and clinical outcomes were compared in the stratification with the presence or absence of allergen sensitisation.ResultsSensitisation rate to moulds and SEs in asthmatic patients was increased when changing the cut-off value of specific IgE titre from 0.35 UA·mL−1 to 0.10 UA·mL−1 (1.7- and 4.5-fold, respectively). Moulds and SEs affected the prevalence of asthma and eosinophilic CRS by interacting with each other. All Type 2 inflammation-related biomarkers except for eosinophils in sinus tissue were significantly higher in patients with mould or SE (mould/SE) sensitisation (≥0.10 UA·mL−1) (n=19) than in those without (n=37) and healthy subjects (all p<0.05). Meanwhile, mould/SE sensitisation did not affect longitudinal changes in clinical outcomes after ESS. Changes in serum mould/SE-IgE levels after ESS remained unclear.ConclusionMould/SE sensitisation (≥0.10 UA·mL−1) may affect the development of Type 2 inflammation and clinical outcomes in CRS patients.

Anisakis simplex products impair intestinal epithelial barrier function and occludin and zonula occludens-1 localisation in differentiated Caco-2 cells.

BackgroundAnisakis spp. are nematode parasites found in a wide range of marine organisms. Human beings may accidentally become infected, showing the symptoms of anisakiasis and allergic responses. There has been evidence of increased intestinal permeability in A. simplex–sensitized subjects and that specific IgE titres increase in some allergic patients when fishery products are re-introduced into their diet. The aims of this work were to study the effect of A. simplex crude extract on the intestinal integrity and permeability by using Caco-2 cell monolayer. To analyse the capacity of Ani s 4 allergen to cross the epithelial barrier.Methodology/Principal findingsCellular bioenergetics, transepithelial electrical resistance, viability, permeability, reactive oxygen species generation and immunofluorescent staining of tight junction proteins were analysed. A. simplex crude extract compromises the Caco-2 cell monolayer integrity in a dose-dependent manner. This effect is detected at 1 hour of culture and integrity is recovered after 24 hours of culture. The epithelial barrier disruption is accompanied by an increase in paracellular permeability and reactive oxygen species production and by a delocalization of occludin and zonula occludens-1. Finally, Ani s 4, a thermostable and resistant to digestion allergen with cystatin activity, is able to cross the epithelial barrier in Caco-2 monolayer and reach a cumulative mean percentage of 22.7% of total concentration in the basolateral side after 24 hours of culture.Conclusions/SignificanceOur results demonstrate that A. simplex induces an early and reversible alteration of integrity and permeability of Caco-2 cell monolayer and that an underlying mechanism of this effect would involve the oxidative stress and disruption of epithelial tight junctions. Additionally, it has been shown that Ani s 4 allergen is able to cross the epithelial barrier. These findings could explain the increased intestinal permeability observed in Anisakis-sensitized patients, the changes over time in IgE sensitization to A. simplex allergens, and the specific IgE persistence in Anisakis allergy.

Diagnosis and Management of Patients with the α-Gal Syndrome

The galactose-α-1,3-galactose (α-Gal) syndrome has many novel features that are relevant to diagnosis and management. In most cases, the diagnosis can be made on a history of delayed allergic reactions to mammalian meat and the blood test for IgE to the oligosaccharide α-Gal. In general, the diagnosis also dictates the primary treatment, that is, avoiding mammalian meat and also dairy in some cases. In the United States, the lone star tick is the primary cause of this disease, but different ticks are responsible in other countries. Blood levels of IgE to α-Gal often drop in patients who avoid recurrent tick bites, but the rate of decline is variable. Similarly, the delay before reactions is variable and the severity of the allergic reactions is not predicted by the delay or the titer of specific IgE. Some mammalian-derived products such as heart valves, gelatin-based plasma expanders, and pancreatic enzymes are relevant to only select patient groups. A minority of cases may benefit from avoiding a wide range of products that are prepared with mammalian-derived constituents, such as gelatin. This review focuses on the nature of the syndrome, common challenges in diagnosis and management, and also gaps in our current knowledge that would benefit from additional investigation.

Investigation into the α-Gal Syndrome: Characteristics of 261 Children and Adults Reporting Red Meat Allergy

Red meat allergy has historically been understood as a rare disease of atopic children, but the discovery of the "α-Gal syndrome," which relates to IgE to the oligosaccharide galactose-α-1,3-galactose (α-Gal), has challenged that notion. To describe the clinical and immunologic characteristics of a large group of subjects with self-reported allergy to mammalian meat. This was an observational study of 261 children and adults (range, 5-82 years) who presented for evaluation for allergic reactions to mammalian meat. Results were based on serum assays and a detailed questionnaire. α-Gal specific IgE ≥ 0.35 IU/mL was detected in 245 subjects and symptom onset occurred ≥2 hours after eating mammalian meat in 211 (81%). Component testing supported a diagnosis of α-Gal syndrome in 95%, pork-cat syndrome in 1.9%, and primary beef allergy in 1.1%. Urticaria was reported by 93%, anaphylaxis by 60%, and gastrointestinal symptoms by 64%. Levels of IgE and IgG specific to α-Gal were similar in subjects who reported early- or delayed-onset symptoms, and in those with and without anaphylaxis. Levels of α-Gal specific IgE and severity of reactions were similar among those with and without traditional atopy, and among children (n= 35) and adults (n= 226). Blood group B trended toward being under-represented among α-Gal-sensitized subjects; however, α-Gal specific IgE titers were high in symptomatic cases with B-antigen. The α-Gal syndrome is a regionally common form of food allergy that has a characteristic but not universal delay in symptom onset, includes gastrointestinal symptoms, can develop at any time in life, and is equally common in otherwise nonatopic individuals.

Randomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg

Background Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children.Methods In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months (n = 21 intervention group) or similar egg free baked goods (n = 22 control group) while maintaining an otherwise egg free diet. The final assessment was a raw egg oral food challenge (OFC) 1 month after ceasing the intervention product. Egg specific IgE and IgG4 were assessed at baseline and 7 months.Results After the intervention there was no difference in raw egg tolerance between groups, (23.5% (4/17) intervention group and 33.3% (6/18) control group). This was independent of age and amount of BE consumed (aOR 0.50 CI 0.11–2.40 p = 0.39). Both groups demonstrated decreased egg specific serum IgE titres and decreased whole egg specific IgE/IgG4 ratios.Discussion We conducted this trial because inclusion of baked egg protein in the diet of egg allergic children appears to move children towards a more tolerant immune profile. Strengths of our study include design of the blinded intervention, the consistent dosing protocol and the regular monitoring of symptoms and intake. However, the study was limited by small sample size resulting in insufficient power to show statistically significant results.Conclusion Our study suggests that short term, regular consumption of BE by BE tolerant 1 to 5 year old children with IgE mediated raw egg allergy may not induce, accelerate or slow development of tolerance to raw egg in this selected population. Trials with larger sample sizes are required to further test this hypothesis.Trial Registration The trial was registered on 7th February 2012 with the Australian New Zealand Clinical Trials Registry (ACTRN 12612000173897).

Immunodominance in allergic T-cell reactivity to Japanese cedar in different geographic cohorts

BackgroundJapanese cedar (JC) pollen is a common trigger for allergic rhinitis in Japan. Pollen proteins targeted by IgE, including Cry j 1 and Cry j 2, and isoflavone reductase (IFR) have been identified. ObjectiveTo compare antigen-specific IgE titers and T-cell responses to JC pollen–derived extract and peptides in cohorts with high and low pollen exposure. MethodsPeripheral blood mononuclear cells from JC pollen allergic or nonallergic patients who have lived in Japan for at least 1 year and JC pollen allergic patients who have never been to Japan were tested for T-cell responses against JC pollen extract and peptide pools derived from Cry j 1, Cry j 2, or IFR. T-cell reactivity was assessed by interleukin 5 and interferon γ production by ELISPOT. ResultsJC pollen–specific T-cell reactivity and IgE titers were significantly higher in the allergic compared with the nonallergic Japanese cohort, which was also associated with different patterns of polysensitization. Interestingly, a significant overlap was observed in the hierarchy of the T-cell epitopes in the allergic Japanese cohort compared with the allergic non-Japanese cohort. In all 3 cohorts, T-cell reactivity was dominantly directed against peptides from the major allergens Cry j 1 and 2, with few T-cell responses detected against IFR. ConclusionOur studies identify common denominators of T-cell reactivity in patient populations with different sensitization patterns, suggesting that generally applicable immunotherapeutic approaches might be developed irrespective of exposure modality.

Relationship between specific IgE to egg components and natural history of egg allergy in Danish children.

The majority of egg-allergic children develop tolerance over time. However, it may take numerous of consecutive egg challenges to get there as no good indices to predict tolerance exist. To investigate whether serial measurements of specific IgE to egg white, ovomucoid, ovalbumin, conalbumin, lysozyme, and egg yolk could improve the specificity of the diagnostic workup and aid in the decision when to rechallenge egg-allergic children. The outcome of oral food challenges with hen's egg and corresponding specific IgE levels were evaluated in children referred to The Allergy Center within an 8-year period. The egg-allergic children were rechallenged and had specific IgE levels measured once a year. During a median follow-up of 26 months, 287 challenges and corresponding 287 serum analyses were performed in 130 children. Of the 130 children, 99 were egg allergic and 82 of these were rechallenged. Based on the initial diagnostic challenges only, area under the curve (AUC) estimates of the ability of specific IgE titers to distinguish between egg sensitization and egg allergy were only modest (maximum 0.83) and provided no clinical meaningful decision points. Specific IgE levels at baseline did not differ between tolerant and persistent allergic children. However longitudinally, acquisition of tolerance was associated with a decrease in IgE to egg white and to ovomucoid. In all cases of an increase in IgE to ovomucoid, the rechallenge was positive. The decision when to rechallenge egg-allergic children should encounter the course of specific IgE.

Determination of specific IgE in pericardial and cerebrospinal fluids in forensic casework

The aim of this study was to characterize total and specific IgE distribution in postmortem serum as well as pericardial and cerebrospinal fluid samples and evaluate the diagnostic usefulness of total and specific IgE determination in pericardial and cerebrospinal fluids in the forensic setting. Three groups were investigated (non-allergic deaths in non-atopic individuals, fatal allergic anaphylaxis deaths and non-allergic deaths in individuals without medical records). In the first group (non-allergic deaths in non-atopic individuals), total IgE concentrations in postmortem serum from femoral blood, pericardial and cerebrospinal fluids were lower than 40, 32 and 11kU/l, respectively. No specific IgE were identified in any of the sampled fluids. In the second group (fatal allergic anaphylaxis deaths), total IgE concentrations in postmortem serum from femoral blood ranged from 139kU/l to 818kU/l, in pericardial fluid from 89kU/l to 622kU/l and in cerebrospinal fluid from 4kU/l to 11kU/l. A positive Phadiatop® test and specific IgE antibodies >0.35kU/l were found exclusively in postmortem serum from femoral blood and pericardial fluid. In the third group (non-allergic deaths in individuals without medical records, possibly including atopic individuals), total IgE concentrations ranged from 42kU/l to 516kU/l in postmortem serum from femoral blood, from 34kU/l to 417kU/l in pericardial fluid and from 3kU/l to 12kU/l in cerebrospinal fluid. A positive Phadiatop® test and specific IgE antibodies >0.35kU/l were found exclusively in postmortem serum from femoral blood and pericardial fluid. These results seem to suggest that total and specific IgE may be measured in postmortem serum from femoral blood and pericardial fluid to estimate total and specific IgE titers at the time of death. Conversely, cerebrospinal fluid total and specific IgE measurement in suspected IgE mediated fatal anaphylaxis cases is of no value for diagnostic purposes.

Changes over Time in IgE Sensitization to Allergens of the Fish Parasite Anisakis spp.

BackgroundSensitization to Anisakis spp. can produce allergic reactions after eating raw or undercooked parasitized fish. Specific IgE is detected long after the onset of symptoms, but the changes in specific IgE levels over a long follow-up period are unknown; furthermore, the influence of Anisakis spp. allergen exposure through consumption of fishery products is also unknown.ObjectiveTo analyse the changes in IgE sensitization to Anisakis spp. allergens over several years of follow-up and the influence of the consumption of fishery products in IgE sensitization.MethodsTotal IgE, Anisakis spp.-specific IgE, anti-Ani s 1 and anti-Ani s 4 IgE were repeatedly measured over a median follow-up duration of 49 months in 17 sensitized patients.ResultsAnisakis spp.-specific IgE was detected in 16/17 patients throughout the follow-up period. The comparison between baseline and last visit measurements showed significant decreases in both total IgE and specific IgE. The specific IgE values had an exponential or polynomial decay trend in 13/17 patients. In 4/17 patients, an increase in specific IgE level with the introduction of fish to the diet was observed. Three patients reported symptoms after eating aquaculture or previously frozen fish, and in two of those patients, symptom presentation was coincident with an increase in specific IgE level.ConclusionsIgE sensitization to Anisakis spp. allergens lasts for many years since specific IgE was detectable in some patients after more than 8 years from the allergic episode. Specific IgE monitoring showed that specific IgE titres increase in some allergic patients and that allergen contamination of fishery products can account for the observed increase in Anisakis spp.-specific IgE level.Clinical RelevanceFollowing sensitization to Anisakis spp. allergens, the absence of additional exposure to those allergens does not result in the loss of IgE sensitization. Exposure to Anisakis spp. allergens in fishery products can increase the specific IgE level in some sensitized patients.

SIX CASES OF WHEAT-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS IN CHILDREN

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is often reported in adults for whom the specific IgE to ω-5 gliadin can be a useful diagnostic test. However, few cases of WDEIA in children have been reported. We herein report six cases (aged 7-16 years) of children with WDEIA, who had no clinical history of immediate-type wheat allergy but who were diagnosed by a wheat ingestion + exercise provocation test. The specific IgE to wheat ranged <0.35-3.49 (median 1.64) UA/ml. Skin prick tests using wheat extract were performed on 3 patients who showed either a negative or low specific IgE titer to wheat, and all of them resulted in negative findings. The specific IgE to ω-5 gliadin was below the detection limit in all cases. Aspirin-supplemented provocation tests were performed to 4 cases who had negative results in the wheat + exercise test. All of these resulted in a positive reaction, and two of them provoked the occurrence of anaphylactic shock, which was relieved by the intramuscular injection of adrenaline. WDEIA in children cannot be ruled out by serological tests alone. On the other hand, severe symptoms might be provoked by the provocation test. Therefore, a safe procedure is warranted for the diagnosis of WDEIA in children.

Safety of Specific Oral Tolerance Induction (SOTI) with Partially Hydrolyzed Cereals in Correlation to Wheat-Protein IgE

A major drawback of specific oral tolerance induction (SOTI) using standard food products is the possibility of severe side effects. The purpose of this study was to correlate safety of SOTI using partially hydrolyzed Cereals (pHC) in children diagnosed for IgE-mediated allergy to wheat with specific IgE titers to various wheat proteins.

Native and denatured egg white protein IgE tests discriminate hen's egg allergic from egg-tolerant children.

Accurate diagnosis of egg allergy by IgE testing is challenged by a large number of atopic subjects sensitized, but clinically tolerant to eggs. In addition, discrimination between allergy to raw only, or raw and cooked egg allergy is important. In this study, we investigate the diagnostic performance of IgE tests to native and denatured egg proteins. According to food challenges and clinical tolerance, study subjects were randomized to the following groups: (Group A) sensitized but clinically tolerant to egg, (Group B) allergic to raw egg only, or (Group C) allergic to raw and cooked egg. Serum-specific IgE to native or reduced and oxidized egg white, ovomucoid, and ovalbumin were measured. Increasing titers of specific IgE to the various proteins were found according to the degree of the egg allergy. Cut-off values for IgE testing to native egg could be determined to distinguish between raw egg allergic and egg-tolerant subjects (1.6 kU/l), as well as raw and cooked egg allergic and egg-tolerant subjects (4.1 kU/l). ROC curves analysis showed that native ovalbumin was the best test for the diagnosis of allergy to raw and cooked egg, and native ovomucoid was best to distinguish between allergy to raw only, and allergy to raw and cooked egg. Sequential testing improved the diagnosis, when in addition to IgE to native egg white, IgE to native ovalbumin was tested for the diagnosis of raw and cooked egg allergy, and IgE to native ovomucoid for the discrimination between allergy to raw only, or to raw and cooked eggs. The diagnosis of egg allergy can be significantly improved using a panel of IgE tests to egg proteins in the native or denatured form. The accuracy can be improved using combined IgE testing.

Diagnostic Decision Points of Specific IgE Titers in Patients With Food Allergy: Are They Appropriate in All Clinical Settings?

In daily clinical practice, it is not so easy to make a confirmative diagnosis of food allergy. Interpretation of skin prick test and serum food-specific IgE (sIgE) test results is influenced by detailed clinical history of an individual patient, but ingested foods which provoke adverse reactions often contain many ingredients and lead to a misdiagnosis of food allergy. Oral food challenge is recommended for the diagnosis of food allergy, but we cannot always perform oral food challenge for various reasons, including recent severe reactions to food, severe atopic dermatitis, patient' and/or parents' refusal and noncooperation of young patients. Thus, from the physician's point of view, cutoff values of sIgE titers that provide high positive and negative predictive values would be very useful in clinical settings because they help determine which patient is more likely to have symptoms in response to a certain food and which are probably nonreactive.

Celiac Disease in a Patient with Baker’s Asthma and Wheat Allergy Due to Tri a 14

We describe the case of a patient that developed persistent severe asthma after having started to work in a bakery. The subsequent appearance of gastrointestinal symptoms was diagnosed as celiac disease (CD). She also experienced severe asthma attacks when cooking pasta, and expe-rienced anaphylactic shock a few minutes after wheat flour inhalation. The allergologic workup was positive for several cereal products and Tri a 14 (Tricum aestivum 14), while specific IgE titer to Pru p 3 (Prunus persica 3) was negative. Our patient had no recurrence of these episodes when she avoided cooking wheat flour products and wheat in processed foods. The pathogenic mechanisms underlying CD and IgE-mediated food allergy are different and the coexistence of both diseases seems to be rare. Tri a 14 is the major wheat allergen involved in our case; this allergen can sensitize through the respiratory and the oral route, and can give way to anaphylaxis. A possible role played by interleukin-15 (IL-15) and interleukin-21 (IL-21) in the induction of IgE-mediate hypersensitivity, as well as in the pathogenesis of CD, is prospected and discussed briefly herein.