Immunoglobulin E Sensitization Research Articles

Sensitization to Food and Aero-Allergens in Children with Coeliac Disease Assessed with the Use of a Multiplex Molecular Diagnostic Technique

(1) Background. Coeliac disease (CD) often co-occurs with autoimmune conditions or genetic syndromes, but there are few studies on the co-existence of CD and immunoglobulin E (IgE)-mediated allergies. The purpose of this study was to assess sensitization to food and aero-allergens in pediatric patients with CD. (2) Methods. A multiplex ALEX®2 test was used to determine specific IgEs (sIgEs). (3) Results. The study included 108 children newly diagnosed with CD. Allergen extract- and/or allergen molecule-sIgEs were detected in 49.1% of children. Most children (41.5%) were sensitized to both inhalant and food allergens. The three most common aero-allergens (timothy pollen, ryegrass, silver birch) were molecules Phl p 1, Lol p 1, and Bet v 1. The most common food allergens (hazelnut, apple, and peanut) were Cor a 1, Mal d 1, and Ara h 8 molecules of the PR-10 subfamily. Patients were not sensitized to cereal allergens containing gluten. Spearman’s rank correlation analysis of sensitized patients showed a significant positive relationship (r = 0.31) between the patients’ age and the occurrence of positive sIgEs (≥0.3 kUA/L) for inhalant allergen molecules (p = 0.045). In sensitized patients, mainly symptoms of inhalant allergy were observed, such as hay fever, conjunctivitis, and bronchial asthma. (4) Conclusions. The current study indicates the co-occurrence of IgE sensitization to food and inhalant allergens in children with CD. The study highlights the need to take a closer look at the diagnosis of IgE-mediated allergy in patients with CD, which may help in their care and lead to a better understanding of the relationship between CD and IgE-mediated allergy.

Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis.

The prevalence of food allergy is rising and is estimated to approach 10%. Red meat allergy is the first known food allergy elicited by immunoglobulin E (IgE) antibodies recognizing a carbohydrate. Due to the loss of function of the alpha-1,3-galactosyltransferase (GGTA1) gene in humans, the disaccharide galactose-α-1,3-galactose (α-Gal) cannot be synthesized and therefore became immunogenic. IgE sensitization is elicited through the skin by repetitive tick bites transmitting α-Gal. The underlying mechanisms regarding innate and adaptive immune cell activation, including the B-cell isotype switch to IgE, are poorly understood, requiring further research and physiologically relevant animal models. Here, we describe a new animal model of red meat allergy using percutaneous α-Gal sensitization of gene-edited GGTA1-deficient pigs. Total and α-Gal-specific IgG, IgG1, IgG2, IgG4, and IgE levels were tracked. Further key factors associated with allergic skin inflammation, type 2 immunity, and allergy development were measured in PBMCs and skin samples. Significant increases in α-Gal-specific IgG1 and IgE levels indicated successful sensitization to the allergen α-Gal. Intracutaneous sensitizations with α-Gal recruited lymphocytes to the skin, including elevated numbers of T helper 2 (Th2) cells. Finally, α-Gal-sensitized pigs not only recognized α-Gal as non-self-antigen following α-Gal exposure through the skin but also developed anaphylaxis upon antigen challenge. Based on the similarities between the porcine and human skin, this new large animal model for α-Gal allergy should help to unveil the consecutive steps of cutaneous sensitization and aid the development of prophylactic and treatment interventions.

Cross-reactive carbohydrate determinants in atopic and healthy dogs and their influence on allergy test specificity.

The selection of allergens for immunotherapy in atopic dogs is often based on serum allergy testing. Cross-reactive carbohydrate determinants (CCDs) are common structures in plant and insect allergens that reportedly induce polysensitisation, reduce agreement between intradermal and serum tests and complicate allergen selection. Thirty-four dogs with diagnosed atopic dermatitis and 10 healthy dogs were included in the study. An intradermal test was conducted in atopic dogs, and serum samples from allergic and healthy dogs were analysed for allergen-specific immunoglobulin E (IgE) before and after inhibition of detectable anti-CCD-IgE antibodies. Anti-CCD-IgE antibodies were not found in any of the healthy dogs and no polysensitisation to plant and insect allergens was detected. The agreement between intradermal and serum allergy test results in the atopic dogs with anti-CCD-IgE antibodies improved from slight to fair after blocking the anti-CCD-IgE antibodies. In addition, blocking clearly reduced polysensitisation to plant allergens but not to acarid allergens. Only a limited number of healthy dogs were tested in this study. A gold standard for determining the clinical relevance of IgE sensitisation does not exist. Inhibition of anti-CCD-IgE antibodies seems to be of importance to improve serum test specificity for allergen-specific IgE in atopic dogs in relation to intradermal allergy testing.

Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow's-Milk-Specific IgE Sensitization.

Immunoglobulin-E(IgE)-mediated hypersensitivity to cow's milk allergens is a frequent cause of severe and life-threatening anaphylactic reactions. Besides case histories and controlled food challenges, the detection of the IgE antibodies specific to cow's milk allergens is important for the diagnosis of cow-milk-specific IgE sensitization. Cow´s milk allergen molecules provide useful information for the refined detection of cow-milk-specific IgE sensitization. A micro-array based on ImmunoCAP ISAC technology was developed and designated milk allergen micro-array (MAMA), containing a complete panel of purified natural and recombinant cow's milk allergens (caseins, α-lactalbumin, β-lactoglobulin, bovine serum albumin-BSA and lactoferrin), recombinant BSA fragments, and α-casein-, α-lactalbumin- and β-lactoglobulin-derived synthetic peptides. Sera from 80 children with confirmed symptoms related to cow's milk intake (without anaphylaxis: n = 39; anaphylaxis with a Sampson grade of 1-3: n = 21; and anaphylaxis with a Sampson grade of 4-5: n = 20) were studied. The alterations in the specific IgE levels were analyzed in a subgroup of eleven patients, i.e., five who did not and six who did acquire natural tolerance. The use of MAMA allowed a component-resolved diagnosis of IgE sensitization in each of the children suffering from cow's-milk-related anaphylaxis according to Sampson grades 1-5 requiring only 20-30 microliters of serum. IgE sensitization to caseins and casein-derived peptides was found in each of the children with Sampson grades of 4-5. Among the grade 1-3 patients, nine patients showed negative reactivity to caseins but showed IgE reactivity to alpha-lactalbumin (n = 7) or beta-lactoglobulin (n = 2). For certain children, an IgE sensitization to cryptic peptide epitopes without detectable allergen-specific IgE was found. Twenty-four children with cow-milk-specific anaphylaxis showed additional IgE sensitizations to BSA, but they were all sensitized to either caseins, alpha-lactalbumin, or beta-lactoglobulin. A total of 17 of the 39 children without anaphylaxis lacked specific IgE reactivity to any of the tested components. The children developing tolerance showed a reduction in allergen and/or peptide-specific IgE levels, whereas those remaining sensitive did not. The use of MAMA allows for the detection, using only a few microliters of serum, of IgE sensitization to multiple cow's milk allergens and allergen-derived peptides in cow-milk-allergic children with cow-milk-related anaphylaxis.

Laboratory Test Results in Patients with Workplace Moisture Damage Associated Symptoms—The SAMDAW Study

The mechanisms of health effects of moisture damage (MD) are unclear, but inflammatory responses have been suspected. The usefulness of laboratory and allergy tests among patients in secondary healthcare with symptoms associated with workplace MD were examined. Full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total serum immunoglobulin E (IgE), fractional exhaled nitric oxide (FeNO), and skin prick testing were assessed and analyzed in relation to multiple chemical sensitivity (MCS) and perceived stress in 99 patients and 48 controls. In analysis, t-tests, Mann-Whitney tests, and chi-squared tests were used. Minor clinically insignificant differences in blood counts were seen in patients and controls, but among patients with asthma an elevated neutrophil count was found in 19% with and only in 2% of patients without asthma (p = 0.003). CRP levels and ESR were low, and the study patients' FeNO, total IgE, or allergic sensitization were not increased compared to controls. The level of stress was high among 26% of patients and 6% of controls (p = 0.005), and MCS was more common among patients (39% vs. 10%, p < 0.001). Stress or MCS were not significantly associated with laboratory test results. In conclusion, no basic laboratory or allergy test results were characteristic of this patient group, and neither inflammatory processes nor allergic sensitization were found to explain the symptoms among these patients. While the value of basic laboratory tests should not be ignored, the use of allergy tests does not seem necessary when symptoms are indicated to be workplace-related.

Qualitative and quantitative comparison of allergen component-specific to birch and grass analyzed by ImmunoCAP assay and Euroline immunoblot test.

Background. In the diagnostic work up of allergy, determining allergen component-specific immunoglobulin E (IgE) is important for diagnosis, prognosis and choice of treatment. Objective. The purpose of this study was to evaluate the performance of the immunoblotting assay (Euroline) in detection of IgE antibodies against timothy grass and birch pollen allergen components compared to fluorescent enzyme assay (ImmunoCAP, Phadia 250). Methods. A total of 128 serum samples from patients allergic to timothy grass and birch pollen were analysed. The levels of IgE antibodies to timothy grass and birch pollen were measured using Euroline DPA-Dx pollen 1 and ImmunoCAP assay. The two methods were then compared on binary (positive vs negative), semi-quantitative (IgE classes) and quantitative (concentration) levels. The two methods were also compared to results from skin prick testing. Results. The Euroline method showed a positive percentage agreement of 93% and negative percentage agreement of 94% with an overall accuracy of 94% when compared to ImmunoCAP. Kappa analysis showed moderate strength of agreement between the methods in determining IgE classes for 7/11 components tested. All components showed a positive correlation when analysed using Spearman's rank correlation. Conclusions. Overall, we found that there is good correlation between the Euroline and ImmunoCAP methods in measuring IgE sensitization.

Using Component-Resolved Diagnosis to Characterize the Sensitization to Specific Cat and Dog Allergens in Patients with Allergic Respiratory Diseases in Catalonia, Spain

Introduction: Sensitization to cat and dog allergens is common in patients with allergic respiratory diseases. The study objective was to determine the prevalence of immunoglobulin E (IgE) sensitization to specific cat and dog allergens using component-resolved diagnosis (CRD) in patients with allergic respiratory diseases plus cat and/or dog sensitization. Methods: We included 87 patients aged 8–62 years, diagnosed with allergic asthma and/or rhinitis plus cat and/or dog sensitization, and attended at the allergy section of a tertiary hospital in Badalona (Catalonia, Spain). We used CRD to determine IgE sensitization to specific cat/dog allergens and skin prick tests (SPTs) to determine differences between diagnostic test results. Results: Patients were monosensitized to cats (20.7%) or dogs (3.4%) or sensitized to both (75.9%). The highest positive allergen rates were for Fel d 1 (91.7%) and Fel d 4 (41%) in patients sensitized to cat allergens and for Can f 5 (80%) and Can f 1 (70%) in those sensitized to dog allergens. CRD and SPT results differed somewhat: 16.1% and 27.6% of patients CRD positive for cat or dog sensitization, respectively, were SPT negative, and 6.9% SPT positive for dog sensitization were CRD negative. Few statistically significant relationships were found between any allergen components and any respiratory disease characteristic or contact with furry animals. Conclusions: CRD may be used to determine the prevalence of IgE sensitization to specific cat and dog allergens in patients with allergic respiratory diseases plus cat and/or dog sensitization. As SPT may not correctly identify all patients sensitized to cats and dogs, our results support the use of CRD.

Molecular sensitization patterns of common food-and respiratory allergens in the Hungarian population

BackgroundRecently developed Immunoglobulin-E (IgE) based molecular allergy diagnostics provide the ability of identifying allergenic components or ingredients at the molecular level (component-resolved-diagnosis, CRD). Compared to the classical IgE-based allergy diagnostics, molecular technology is providing more sensitive and specific IgE-sensitization patterns. Certain sensitization patterns are characteristic of large geographic regions. There are only few data available on the molecular IgE sensitization patterns in East-Central Europe. This study aims to present further data from this region. MethodsData of 3993 stored, anonymized molecular ImmunoCap IgE measurements (CRD), performed in Hungary between January-December 2019 from sera of 1288 subjects (mean age: 27 years ±18 years, male/female ratio 0.56) were analyzed retrospectively, in order to get a local distributional pattern of the sensitizing (IgE >0.35 KU/l) molecular allergens. ResultsThe proportion of CRD positive cases was 24.3%. Amongst them, the most prevalent inhalative allergens were Amb a 1 (18%) Art v 1 (8%) in adults and Der p 2 (3%) and Der p 1 (3%) and Amb a 1 (4%) in subjects below 18 years of age. The same for food allergens were Gal d 2 (21%), Bos d 4 (17%), Bos d 5 (11%) in adults and Gal d 2 (38%), Gal d 1 (28%), Bos d 4 (21%), Bos d 5 (13%) and Bos d 8 (7%) in children. The ratio of mono-sensitivities among CRD-positive cases was 37.5%. ConclusionOur results provide region-specific patterns of sensitization and molecular allergen spreading for Hungary. The relatively higher abundance of polysensitization's among allergic cases underlines the need for early diagnostic -and preventive measures in the future.

Longitudinal changes in body mass index Z-scores during infancy and risk of childhood allergies.

Few studies address the dynamic changes of body mass index (BMI) Z-scores during infancy with breastfeeding and their impact on childhood atopic diseases. A total of 183 children from a birth cohort regularly followed-up for 4 years were enrolled in this study. Time series data of BMI Z-scores from 1 month to 2 years of age was clustered using K-means method in R software. Breastfeeding status during the first 6 months of life was recorded and classified. The total serum and specific immunoglobulin E (IgE) levels to food and inhalant allergens were measured at age 0.5, 1, 1.5, and 2 years. Using K-means clustering, the dynamic changes in BMI Z-scores were classified into three clusters (cluster A, increasing, n=62; cluster B; decreasing, n=62; cluster C, constant low, n=59). Despite having no statistical association with atopic diseases, a decreasing trend in infantile BMI Z-scores was significantly associated with a higher prevalence of IgE sensitization at age 1 which increased the risk of rhinitis development at age 4 (P=0.007). No difference in BMI Z-scores was determined between different breastfeeding patterns. However, exclusive formula feeding ≥6 months was found to be significantly associated with mite sensitization at age 1.5 years which risks asthma development at age 4 (P=0.001). A decreasing trend of BMI Z-scores during infancy is determined to be inversely associated with IgE and allergen sensitization, which may potentially increase the risk of allergies in early childhood.

Allergic Asthma in the Era of Personalized Medicine.

Allergic asthma is the most common asthma phenotype and is characterized by IgE sensitization to airborne allergens and subsequent typical asthmatic symptoms after exposure. A form of type 2 (T2) airway inflammation underlies allergic asthma. It usually arises in childhood and is accompanied by multimorbidity presenting with the occurrence of other atopic diseases, such as atopic dermatitis and allergic rhinitis. Diagnosis of the allergic endotype is based on in vivo (skin prick tests) and/or in vitro (allergen-specific IgE levels, component-resolved diagnosis (CRD)) documentation of allergic sensitization. Biomarkers identifying patients with allergic asthma include total immunoglobulin E (IgE) levels, fractional exhaled nitric oxide (FeNO) and serum eosinophil counts. The treatment of allergic asthma is a complex procedure and requires a patient-tailored approach. Besides environmental control involving allergen avoidance measurements and cornerstone pharmacological interventions based on inhaled drugs, allergen-specific immunotherapy (AIT) and biologics are now at the forefront when it comes to personalized management of asthma. The current review aims to shed light on the distinct phenotype of allergic asthma, ranging over its current definition, clinical characteristics, pathophysiology and biomarkers, as well as its treatment options in the era of precision medicine.

Molecular Allergen-Specific IgE Recognition Profiles and Cumulative Specific IgE Levels Associated with Phenotypes of Cat Allergy.

Cat allergy is a major trigger factor for respiratory reactions (asthma and rhinitis) in patients with immunoglobulin E (IgE) sensitization. In this study, we used a comprehensive panel of purified cat allergen molecules (rFel d 1, nFel d 2, rFel d 3, rFel d 4, rFel d 7, and rFel d 8) that were obtained by recombinant expression in Escherichia coli or by purification as natural proteins to study possible associations with different phenotypes of cat allergy (i.e., rhinitis, conjunctivitis, asthma, and dermatitis) by analyzing molecular IgE recognition profiles in a representative cohort of clinically well-characterized adult cat allergic subjects (n = 84). IgE levels specific to each of the allergen molecules and to natural cat allergen extract were quantified by ImmunoCAP measurements. Cumulative IgE levels specific to the cat allergen molecules correlated significantly with IgE levels specific to the cat allergen extract, indicating that the panel of allergen molecules resembled IgE epitopes of the natural allergen source. rFel d 1 represented the major cat allergen, which was recognized by 97.2% of cat allergic patients; however, rFel d 3, rFel d 4, and rFel d 7 each showed IgE reactivity in more than 50% of cat allergic patients, indicating the importance of additional allergens in cat allergy. Patients with cat-related skin symptoms showed a trend toward higher IgE levels and/or frequencies of sensitization to each of the tested allergen molecules compared with patients suffering only from rhinitis or asthma, while there were no such differences between patients with rhinitis and asthma. The IgE levels specific to allergen molecules, the IgE levels specific to cat allergen extract, and the IgE levels specific to rFel d 1 were significantly higher in patients with four different symptoms compared with patients with 1–2 symptoms. This difference was more pronounced for the sum of IgE levels specific to the allergen molecules and to cat extract than for IgE levels specific for rFel d 1 alone. Our study indicates that, in addition to rFel d 1, rFel d 3, rFel d 4, and rFel d 7 must be considered as important cat allergens. Furthermore, the cumulative sum of IgE levels specific to cat allergen molecules seems to be a biomarker for identifying patients with complex phenotypes of cat allergy. These findings are important for the diagnosis of IgE sensitization to cats and for the design of allergen-specific immunotherapies for the treatment and prevention of cat allergy.

Serum IgE profiles in Chinese pollinosis patients with grass pollen sensitisation

PurposePollen from trees, grasses, and weeds is a common allergen source. The characteristics of pollen allergy in China are obviously different from Europe. Most studies have focused on tree and weed pollen, but there is a paucity of data on grass pollen sensitisation in China. Therefore, we used component-resolved diagnostics to investigate the serum-specific immunoglobulin E (sIgE) to grass pollen in Chinese patients with pollinosis. MethodsWe retrospectively analysed 547 patients with pollen allegy from an outpatient Allergy Department in Beijing, China. All the patients answered questionnaires about their clinical allergy histories. Total immunoglobulin E (IgE) and sIgE levels to grass pollen (Bermuda, Timothy grass) were quantified by ImmunoCAP using 0.35 kUA/L as a threshold for positivity. ResultsOf the 547 pollinosis patients, 389 (71.1%) showed a positive sIgE reaction to either grass pollen, or both. The prevalence of food allergy was significantly lower in patients with grass pollen sensitisation. Among the 389 patients with grass pollen sensitisation, the prevalence of sIgE to allergen extracts of bermuda, mugwort, ragweed, plane, hop, ash, birch, and timothy grass was 97%, 96%, 94%, 88%, 88%, 84%, 78%, and 78%, respectively. However, only 134/389 (34%) were positive for Cyn d 1, 29/389 (7%) for Phl p 1, and 8/389 (2%) for Phl p 5b. For pollinosis patients, 62/547 (11%) were sIgE-positive for cross-reactive carbohydrate determinants (CCDs), and their grass pollen-sIgE was also positive. ConclusionsThe prevalence of in vitro IgE sensitisation to grass pollen extract is high in Chinese patients with pollinosis. But mostly spurious and characterized by IgE sensitisation to profilins and CCD, induced by other pollen. Component-resolved diagnostics is an extremely useful tool precise diagnostics of pollen allergy in China.

Food Protein-Induced Allergic Proctocolitis May Have Distinct Phenotypes

To investigate the prevalence of immunoglobulin E (IgE) sensitization and transition to IgE-mediated allergy to the culprit food or other concomitant foods in infants with food protein-induced allergic proctocolitis (FPIAP).In this retrospective study, we included 204 infants with confirmed FPIAP, evaluated between January 2015 and December 2018 at Hacettepe University, in Ankara, Turkey.Infants were categorized into 3 groups on the basis of clinical history, serum immunoglobulin E (sIgE) levels, and skin-prick tests (SPTs). Group 1 was those with FPIAP with or without IgE-mediated food hypersensitivity to offending and “nonoffending” foods at the initial consultation (n = 180). Group 2 was those with FPIAP with IgE sensitization but no clinical hypersensitivity symptoms to offending foods at onset or during study follow-up (n = 17), and group 3 was those with FPIAP with no sensitization at onset but who had a later transition to IgE-mediated hypersensitivity at follow-up (n = 7).FPIAP onset occurred at a median age of 2 months (25% to 75%; interquartile range [IQR]: 1.0–3.0). Milk was the trigger for 62.7% (n = 128). In 36.7% (n = 75), the trigger was milk plus other foods, and 0.5% (n = 1) had a trigger that was not milk. Children developed tolerance at a median of 12 months (IQR: 10.0–14.0). Among 180 infants in group 1, 86% (n = 156) did not show IgE to any food, 7.7% (n = 14) had IgE sensitization to offending foods at the initial consultation, and 9 of these 14 patients had symptoms of both IgE-mediated allergy and FPIAP to cow’s milk (CM) and egg white at onset of FPIAP. The median age of tolerance in group 1 was 11 months (IQR: 10–14]. Group 2 had sensitization to FPIAP triggering foods but no symptoms of IgE-mediated allergy. Twelve had positive SPT or sIgE to CM, 3 were positive to egg, and 3 had positive test results to CM and egg (the median sIgE to CM was 0.5 kUA/L; the median IgE to egg was 2.1 kUA/L at FPIAP onset). The median age of tolerance to FPIAP trigger foods in group 2 was 11 months (IQR: 9.5–12). Group 3 developed IgE-mediated symptoms to trigger foods at a median age of 5 months (IQR: 5–6). The median age of tolerance to IgE-mediated FPIAP triggering foods was 19 months (IQR: 18.0–29.0). Children with multiple food FPIAP developed tolerance later than those with single-food FPIAP (the median age for multiple food FPIAP groups was 13 months [IQR: 11–16] versus that of single-food FPIAP, which was 11 months [IQR: 10–13]; P < .001).On the basis of this study, some infants with FPIAP may transition to different food allergy clinical phenotypes, including IgE-mediated hypersensitivity to FPIAP triggering foods. Although all infants in the study developed tolerance, there was a delay in tolerance development among infants who transitioned to IgE-mediated hypersensitivity, compared with that of other groups. Those with multiple food FPIAP also had delayed tolerance when compared with infants with single-food FPIAP.Because of the retrospective nature, the strength of the conclusions are limited by a lack of systematic timing of challenge to trigger foods in infants with FPIAP and IgE-mediated allergy. Nonetheless, this information can be useful in counseling families regarding the likely time to resolution when concomitant IgE-mediated symptoms occur in individuals initially diagnosed with FPIAP and those with multiple food FPIAP. Unfortunately, they were not able to determine risk factors for development of IgE-mediated allergy in these infants with FPIAP. Further prospective studies are needed.

Risk Factors Influencing Tolerance and Clinical Features of Food Protein-Induced Allergic Proctocolitis

To examine the clinical course and risk factors of food protein-induced allergic proctocolitis (FPIAP).A total of 257 infants who presented to 5 outpatient pediatric allergy or gastroenterology clinics with rectal bleeding and were given a diagnosis of FPIAP were included in the study.After enrollment, infants had serum immunoglobulin E testing, skin-prick testing (SPT), and complete blood cell count. Clinical characteristics were prospectively managed. Patients with other known gastrointestinal illnesses were excluded. Cow’s milk elimination was trialed first in both the infant’s diet as well as the mother’s diet if breastfeeding, and, if no improvement, egg was eliminated next. Combined elimination of wheat, nuts, and soy followed, if no improvement. Eliminated foods were then reintroduced after 2 to 4 weeks, and a worsening of symptoms confirmed diagnosis.There was no sex predominance, with 50.2% being female (n = 129). The vast majority were breastfed at diagnosis (97.2%), with 66.5% exclusively breastfed. Blood in stool was present in every case, and other common complaints were mucous in stool (n = 224) and loose stool (n = 168). Cow’s milk was the most common causative food, accounting for 99.2% of cases. Comparing those with only 1 food allergy (75.9%) versus those with multiple food allergies, children with a single-food allergy more often were exclusively breastfeeding at diagnosis, had a longer duration of breastfeeding, had less antibiotic use in the first 6 months, and had higher tolerance development (P = .003, < 0.001, < 0.001, and < 0.001, respectively). Immunoglobulin E (IgE) sensitization was assessed in 239 patients, and 55 (23%) had positive test results. Sensitized children less often developed tolerance to the offending allergen compared with nonsensitized children (52.4% versus 81.2%). Only 16 patients underwent endoscopy and were continued to be treated as having FPIAP.Most patients with FPIAP resolve within a year. Infants with colic, IgE sensitization, and multiple food allergies may be at risk for delayed tolerance. Cow’s milk should be the first excluded food in infants and breastfeeding mothers, and elimination should resolve symptoms in most patients. Breastfeeding and lower antibiotic use was associated with a decrease in the development of multiple food allergies. The role of SPT and IgE testing is still unclear and may not add benefit to most cases. Endoscopy did not change management, even in severe cases.This is an important study that characterizes a common condition. The prospective nature of this study is a strength, along with high retention of subjects throughout the study. The involvement of multiple centers and specialties introduced some variability in practice. More severe cases of FPIAP are likely represented in this study because subjects had referral to allergy or gastroenterology specialists. Also, the high prevalence of breastfeeding in this cohort may limit its generalizability to other communities; regional food preferences and breastfeeding prevalence may have a large effect on the development of allergies and food sensitization.

Single-Dose Oral Challenges to Validate Eliciting Doses in Children With Cow’s Milk Allergy

To validate the predicted ED05 for cow’s milk, which is the allergen dose that elicits an objective reaction in 5% of a population, of 0.5 mg of cow’s milk protein (0.015 mL of fresh cow’s milk).The study included 182 children between the ages of 6 months and 17 years recruited from 4 centers in the United Kingdom, Ireland, and Spain. Inclusion criteria varied across centers. Participants had to have cow’s milk allergy (CMA), defined by either a clinical history and immunoglobulin E (IgE) sensitization and/or positive food challenge result.The participants were given 0.5 mg of milk protein as either a single unblinded administration or the first dose of a double-blind placebo-controlled food challenge, depending on the center. The predetermined objective criteria for a positive oral food challenge were standardized among centers and included urticaria, angioedema, or rhinoconjunctivitis symptoms that persisted for at least 5 minutes or anaphylaxis. To ensure that all participants had confirmed CMA, clinical reactivity to cow’s milk was assessed in participants >1 year of age by food challenge and in those <1 year of age by history of an allergic reaction within 2 months of the study visit and the presence of IgE sensitization to cow’s milk. Blood samples and skin-prick testing were used to confirm the presence of IgE to cow’s milk in all participants. The proportion of participants reacting to 0.5 mg cow's milk protein was estimated with 2-sided exact 95% confidence intervals (CIs).Of the 182 children who met the inclusion criteria, 10 were excluded because they did not have clinical reactivity when undergoing the confirmatory milk challenge. Of the remaining 172 participants with confirmed clinical reactivity to cow’s milk who underwent the ED05 0.5 mg cow’s milk protein oral food challenge, objective symptoms that met the predetermined positive challenge criteria were observed in 7% (95% CI: 3.7% to 11.9%). One participant (17 years old) experienced chest tightness, wheezing, a drop in peak expiratory-flow rate, and truncal erythema and was treated with epinephrine. All other reactions were mild and did not require treatment. No predictors of reactivity to 0.5 mg cow's milk protein were identified.In this study population, 7% of participants reacted to the proposed eliciting dose of 0.5 mg of cow’s milk protein, leading the authors to conclude that 0.5 mg could be a threshold amount of cow’s milk protein to inform food product allergy labeling for cow’s milk content.Although clear food labeling regarding allergen content and risk of allergic reaction is key to ensuring that those with CMA do not overly restrict their diets (while ensuring that they are protected from having a serious allergic reaction), establishing an ED05 to guide food labeling is challenging because of the striking heterogeneity in clinical reactivity among children with CMA. In this study, the authors highlight these challenges because 1 participant experienced an anaphylactic reaction, which translates to 0.5% of the study population. This observation suggests that if foods that contained ≤0.5 mg cow’s milk protein per serving were labeled as safe and children with CMA ate those foods on a regular basis, we might expect to see many cases of anaphylaxis. However, there is a substantial degree of uncertainty around the 0.5% estimate because the 95% CI ranges from 0.01% to 3.2%, highlighting the fact that much larger studies will be needed to have greater certainty about the expected incidence of anaphylaxis to this dose of cow’s milk protein. Additionally, in the study, the researchers found that as many as 12% of similar children would react to 0.5 mg, which, rather than validating an ED05 of 0.5 mg, suggests that the true ED05 may be <0.5 mg. These aforementioned challenges to identifying an ED05 are further complicated by the fact that there were no predictors of reactivity to the 0.5 mg dose. Nevertheless, more work is needed in this area because the current approach to food labeling is confusing and challenging for patients with CMA and their families to navigate.

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack

Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.

Preterm birth reduces the risk of IgE sensitization up to early adulthood: A population-based birth cohort study.

Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens. To study IgE sensitization to common allergens by gestational age from childhood up to early adulthood. Population-based birth cohort, data from the Swedish BAMSE study were used. Allergen-specific IgE antibodies to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24years. Sensitization was defined as allergen-specific IgE ≥0.35kUA /L to fx5 and/or Phadiatop at each time point.Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA. In BAMSE, 3522 participants were screened for IgE antibodies during follow-up; of these, 197 (5.6%) were born preterm (<37gestational weeks) and 330 (9.4%) post-term (≥42weeks). Preterm birth reduced the risk of sensitization to common food and/or inhalant allergens up to early adulthood by 29% (overall aOR=0.71; 95% CI: 0.52-0.98), and to food allergens specifically by 40% (overall aOR=0.60; 95% CI: 0.38-0.93). No relation was found between post-term birth and IgE sensitization at any time point. Replication analyses in STOPPA (N=675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR=0.72; 95% CI: 0.42-1.21), which resulted in a combined meta-analysis aOR=0.71 (95% CI: 0.54-0.94). Our study suggests an inverse association between preterm birth and long-term IgE sensitization.

The Molecular Allergen Recognition Profile in China as Basis for Allergen-Specific Immunotherapy.

Approximately 30% of the world population suffers from immunoglobulin-E (IgE)-mediated allergy. IgE-mediated allergy affects the respiratory tract, the skin and the gastrointestinal tract and may lead to life-threatening acute systemic manifestations such as anaphylactic shock. The symptoms of allergy are mediated by IgE-recognition of causative allergen molecules from different allergen sources. Today, molecular allergy diagnosis allows determining the disease-causing allergens to develop allergen-specific concepts for prevention and treatment of allergy. Allergen-specific preventive and therapeutic strategies include allergen avoidance, vaccination, and tolerance induction. The implementation of these preventive and therapeutic strategies requires a detailed knowledge of the relevant allergen molecules affecting a given population. China is the world´s most populous country with around 1.4 billion inhabitants and an estimated number of more than 400 million allergic patients. Research in allergy in China has dramatically increased in the last decade. We summarize in this review article what is known about the dominating allergen sources and allergen molecules in China and what further investigations could be performed to draw a molecular map of IgE sensitization for China as a basis for the implementation of systematic and rational allergen-specific preventive and therapeutic strategies to combat allergic diseases in this country.

Atopic respiratory diseases and IgE sensitization are associated with leukocyte subset concentrations in 14,440 blood donors

Background and aimsAllergic rhinitis (AR), allergic conjunctivitis (AC), and asthma are characterized by activation of the immune system. The aim of this study was to explore the long-term association between AR, AC, asthma, and specific immunoglobulin E (IgE) and blood platelet and leukocyte differential counts. Material and methodsIn the Danish Blood Donor Study, 14,440 participants from Central Denmark Region had platelet and leukocyte differential counts available and completed a questionnaire regarding AR, AC, and asthma. Of these participants, 8485 were tested for IgE to inhalation allergens. ResultsThe prevalence of AR, AC, asthma, and IgE sensitization was 19%, 15%, 9%, and 29%, respectively. AR, AC, asthma, wheeze, and IgE sensitization was associated with increased blood eosinophil concentration even in IgE sensitized participants who did not report any allergy or asthma. The strongest associations were observed for participants with current disease. We found no differences in eosinophil concentration between months without symptoms and months with symptoms of AR and asthma. ConclusionAR, AC, asthma, wheezing, and IgE sensitization to inhalation allergens are associated with increased eosinophil concentration. This may reflect a persistent inflammation even in periods without symptomatic disease.

Effect of congenital heart disease on the recurrence of cough variant asthma in children

BackgroundThe research into the recurrence of cough variant asthma (CVA) in congenital heart disease (CHD) are few in number. The purpose of this study is to investigate the effect of CHD on the risk of the recurrence of CVA.MethodsThis study was a retrospective cohort study of 489 children with CVA aged between one and 14 years, of whom 67 had CHD complicated with CVA and 134 had CVA without CHD at a ratio of 1:2 according to age, sex and index year. The adjusted hazard ratio (aHR) of CVA recurrence in both the CHD cohort and the non-CHD cohort was determined by multivariate analysis using the Cox proportional hazard regression model.ResultsAdjusting for CHD classification, Mycoplasma pneumonia (MP) infection and immunoglobulin E (IgE) sensitization, the recurrence hazard of CVA in the complex congenital heart disease (CCHD) group (aHR = 3.281; 95% CI 1.648–6.530; P < 0.01) was significantly higher than that in the simple congenital heart disease group (aHR = 2.555; 95% CI 1.739–3.752; P < 0.01). Further, children with IgE sensitization (aHR = 2.172; 95% CI 1.482–3.184; P < 0.01) had a higher recurrence hazard of CVA than those without IgE sensitization, and children with MP infection (aHR = 1.777; 95% CI 1.188–2.657; P < 0.01) had a higher recurrence hazard of CVA than those without the MP infection.ConclusionThe hazard of recurrent CVA is higher in children with CHD, especially in the CCHD children. In addition, those children with IgE sensitization or a MP infection had an increased hazard of recurrent CVA.