Asymptomatic Sensitization Research Articles

Venom Component Allergen IgE Measurement in the Diagnosis and Management of Insect Sting Allergy

Accurate identification of the allergy-eliciting stinging insect(s) is essential to insuring effective management of Hymenoptera venom-allergic individuals with venom-specific immunotherapy (VIT). Diagnostic testing using whole venom extracts with skin tests and serological-based analyses remains the first level of discrimination for honeybee versus vespid venom sensitization in clinical history-positive patients. As a second-level evaluation, serological testing using molecular venom allergens can further discriminate genuine sensitization (honeybee venom: Api m 1, 3, 4, and 10 versus yellow jacket venom/Polistes dominula venom Ves v 1/Pol d 1 and Ves v 5/Pol d 5) from inter-species cross-reactivity [hyaluronidases (Api m 2, Ves v 2, Pol d 2) and dipeptidyl peptidases IV (Api m 5, Ves v 3, Pol d 3)]. Clinical laboratories use a number of singleplex, oligoplex, and multiplex immunoassays that employ both extracted whole venom and molecular venom allergens (highlighted above) for confirmation of allergic venom sensitization. Established quantitative singleplex autoanalyzers have general governmental regulatory clearance worldwide for venom allergic patient testing with maximally achievable analytical sensitivity (0.1 kUA/L) and confirmed reproducibility (inter-assay CVs<10%). Emerging oligo- and multiplex (fixed panel) assays conserve on serum and are more cost-effective, but they need regulatory clearance in some countries and are prone to higher rates of detecting asymptomatic sensitization. Ultimately, the patient’s clinical history, combined with the proof of sensitization, is the final arbiter in the diagnosis of Hymenoptera venom allergy.

IgE-Mediated Allergy and Asymptomatic Sensitization to Cannabis Allergens-Review of Current Knowledge and Presentation of Six Cases.

Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population.

High burden of clonal mast cell disorders and hereditary α-tryptasemia in patients who need Hymenoptera venom immunotherapy.

In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT. 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3-4 vs. 11% [n = 78 of 709] with Grade 1-2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3-4 vs. 0.001% [n = 78] in Grade 1-2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01). By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.

Аллергия на латекс

Latex, made from Hevea brasiliensis sap, is the material used to make many medical products, including catheters, balloons and gloves. Hundreds of allergens from natural rubber latex have been identified, and 15 of them were numbered, from Hev b1 to Hev b15. Natural proteins in rubber cause both asymptomatic sensitization and type I IgE-mediated hypersensitivity. Treatment of latex makes use of chemical antioxidants that can also bring about type IV hypersensitivity reactions. Latex allergy is one of the most common causes of anaphylaxis in the operating room, and its prevalence has been growing since 1980s, together with the popularity of latex gloves. It is a well-known problem among medical professionals, with gloves and inhaled aerosol particles being the sources thereof. This study aimed to review the current scientific research and practical data in this only partially investigated area. In addition, increasing the awareness of doctors and patients minimizes the existing risks of latex allergy.

The herbicides glyphosate and glufosinate and the cyanotoxin β-N-methylamino-l-alanine induce long-term motor disorders following postnatal exposure: the importance of prior asymptomatic maternal inflammatory sensitization

BackgroundPrenatal maternal immune activation (MIA) and/or perinatal exposure to various xenobiotics have been identified as risk factors for neurological disorders, including neurodegenerative diseases. Epidemiological data suggest an association between early multi-exposures to various insults and neuropathologies. The “multiple-hit hypothesis” assumes that prenatal inflammation makes the brain more susceptible to subsequent exposure to several kinds of neurotoxins. To explore this hypothesis and its pathological consequences, a behavioral longitudinal procedure was performed after prenatal sensitization and postnatal exposure to low doses of pollutants.MethodsMaternal exposure to an acute immune challenge (first hit) was induced by an asymptomatic lipopolysaccharide (LPS) dose (0.008 mg/kg) in mice. This sensitization was followed by exposing the offspring to environmental chemicals (second hit) postnatally, by the oral route. The chemicals used were low doses of the cyanotoxin β-N-methylamino-l-alanine (BMAA; 50 mg/kg), the herbicide glufosinate ammonium (GLA; 0.2 mg/kg) or the pesticide glyphosate (GLY; 5 mg/kg). After assessing maternal parameters, a longitudinal behavioral assessment was carried out on the offspring in order to evaluate motor and emotional abilities in adolescence and adulthood.ResultsWe showed that the low LPS immune challenge was an asymptomatic MIA. Even though a significant increase in systemic pro-inflammatory cytokines was detected in the dams, no maternal behavioral defects were observed. In addition, as shown by rotarod assays and open field tests, this prenatal LPS administration alone did not show any behavioral disruption in offspring. Interestingly, our data showed that offspring subjected to both MIA and post-natal BMAA or GLA exposure displayed motor and anxiety behavioral impairments during adolescence and adulthood. However, this synergistic effect was not observed in the GLY-exposed offspring.ConclusionThese data demonstrated that prenatal and asymptomatic immune sensitization represents a priming effect to subsequent exposure to low doses of pollutants. These double hits act in synergy to induce motor neuron disease-related phenotypes in offspring. Thus, our data strongly emphasize that multiple exposures for developmental neurotoxicity regulatory assessment must be considered. This work paves the way for future studies aiming at deciphering cellular pathways involved in these sensitization processes.

Continuous consumption of whey protein affects motor and cognitive functions in a mouse model of cow’s milk hypersensitivity

Abstract Hypersensitization to a food allergen can occur in the absence of immediate allergic reactions, a condition referred to as asymptomatic sensitization. Using mice asymptomatically sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), we have previously shown that chronic exposure to the allergen results in behavior changes with increased neuroinflammation and cortical demyelination. However, whether allergen avoidance can resolve these pathologies is unknown. Thus, we aimed to compare immunological and behavioral changes in sham- or BLG-sensitized mice with or without the removal of dietary whey after the mice had consumed either a control diet (CTL) or a whey-protein-containing diet (WP) for 2 weeks. As previously reported, BLG-sensitized mice did not display overt physical reactions during the 2-week allergen exposure period, while their plasma levels of BLG-specific IgE and IgG1 were elevated compared to the respective sham groups. Following an additional 2 weeks on either the CTL or WP diet, these antibodies remained elevated in some of the sensitized mice in both diet groups. The grip-strength test indicated that sham mice that switched to the CTL diet after the 2-week WP diet increased limb strengths. In contrast, BLG-sensitized mice on either diet, as well as sham mice that stayed on the WP diet, showed a decline in limb strengths, suggesting that WP consumption, whether during sensitization or as part of the daily diet, affected their motor function. Furthermore, removing dietary WP improved spatial memory performance with the cross-maze test in both sham and BLG-sensitized mice. These results suggested that continuous exposure to a dietary allergen may influence motor and cognitive functions. Supported by grants from NIH (R01 AI168563)

Improving Deproteinization in Colombian Latex from Hevea brasiliensis: A Bibliometric Approximation.

Natural Rubber Field Latex (NRFL) allergens restrict its use in some markets due to health-threatening allergic reactions. These molecules are proteins that are related to asymptomatic sensitization and hypersensitivity mediated by immunoglobulin E (IgE). Although NRFL allergens have been investigated since the 1980s, there are still gaps in knowledge regarding the development of deproteinized natural rubber (DPNR). Therefore, in this study, the deproteinization of NRFL from the lower basin of the Cauca River, Antioquia-Colombia was evaluated using eight systems. The highest removal value was 84.4% and was obtained from the treatment containing SDS (Sodium dodecyl sulfate), Urea, and Ethanol. It was also possible to determine that at high concentrations of SDS, removal percentages higher than 70% are reached. On the other hand, all deproteinizing systems decreased NRFL Zeta potentials without self-coagulation, suggesting enhanced colloidal stability in DPNR latex. On the other hand, the bibliometric analysis presented technological advances in DPRN through different parameters and bibliometric networks. The analysis presented makes an important contribution from the bibliometric approach that could be positive for the development of research on DPNR.

Asymptomatic sensitization to a cow's milk protein induces sustained neuroinflammation and behavioral changes with chronic allergen exposure.

Mouse models of food allergy have contributed to our understanding of various aspects of the disease, including susceptibilities, symptom spectra, cellular mechanisms, and therapeutic approaches. Previously, we used a mouse model of non-anaphylactic cow’s milk allergy (CMA) and investigated sex- and strain-dependent differences in immunological, neurological, and behavioral sequelae. We showed that male C57BL/6J mice sensitized to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5), exhibited anxiety- and depression-like behavior upon acute allergen challenge. Systemic levels of BLG-specific immunoglobulins, cytokines and chemokines were also elevated in the sensitized mice. Furthermore, neuroinflammation and intestinal dysbiosis were evident as the possible causes of the altered behavior. To assess whether frequent allergen exposure influences CMA-associated pathologies over an extended period in this subclinical model, we placed BLG-sensitized mice on a whey protein (WP)-containing or whey-free control (CTL) diet for 3 months. As expected, allergen-specific IgE was significantly elevated in the plasma after completing the 5-week sensitization phase. However, the IgE levels declined in both diet groups after 3 months. In contrast, allergen-specific IgG1 stayed elevated in sensitized mice with the CTL diet, and the WP diet to a lesser extent. Interestingly, BLG-sensitized mice on the WP diet exhibited anxiety-like behavior and a trend toward spatial memory decline compared to the sham or the sensitized mice on the CTL diet. Moreover, increased immunoreactivities for GFAP and Iba1 and elevated levels of CXCL13 and CCL12, the chemokines involved in central leukocyte recruitment and other neurological diseases, were also observed in the brain. We demonstrated that sensitization to the whey protein, particularly with continuous allergen exposure, resulted in persistent neuroinflammation and associated behavioral changes despite lowered allergen-specific immunoglobulin levels. These results suggested that continuous consumption of the offending allergen may lead to adverse consequences in the brain even after desensitization.

Recent advances in the diagnosis and management of tree nut and seed allergy.

Tree nut (TN) and seed allergies are frequent, and their prevalence appears to be on the rise. Allergic reactions associated with these foods are more frequently severe, and these allergies tend to persist into adulthood, consequently affecting quality of life. In this review, we summarize recent advances in diagnostic modalities and management strategies for TN/seed-allergic patients. Clinical manifestations of TN and seed allergy range from asymptomatic sensitization to severe anaphylactic reactions. The use of emerging diagnostic tools such as component resolved diagnostics (CRD) and the basophil activation test (BAT) can help better predict clinical reactivity, the latter being currently reserved for research settings. Strict avoidance of all TN is generally not required, as most patients can tolerate select TN despite co-sensitization. Oral immunotherapy (OIT) is a promising alternative treatment instead of complete avoidance of culprit allergens, as it can safely increase the allergy threshold. Our recent understanding of co-reactivity between various TN and seeds has shaped management opportunities, including select TN introduction and optimization of OIT, two strategies which may improve quality of life. There is a need for better minimally invasive diagnostic methods for TN and seed allergy, with CRD and BAT being promising tools.

Basophil Activation Test Utility as a Diagnostic Tool in LTP Allergy.

Plant-food allergy is an increasing problem, with nonspecific lipid transfer proteins (nsLTPs) triggering mild/severe reactions. Pru p 3 is the major sensitizer in LTP food allergy (FA). However, in vivo and in vitro diagnosis is hampered by the need for differentiating between asymptomatic sensitization and allergy with clinical relevance. The basophil activation test (BAT) is an ex vivo method able to identify specific IgE related to the allergic response. Thus, we aimed to establish the value of BAT in a precise diagnosis of LTP-allergic patients. Ninety-two individuals with peach allergy sensitized to LTP, Pru p 3, were finally included, and 40.2% of them had symptoms to peanut (n = 37). In addition, 16 healthy subjects were recruited. BAT was performed with Pru p 3 and Ara h 9 (peanut LTP) at seven ten-fold concentrations, and was evaluated by flow cytometry, measuring the percentage of CD63 (%CD63+) and CD203c (%CD203chigh) cells, basophil allergen threshold sensitivity (CD-Sens), and area under the dose–response curve (AUC). Significant changes in BAT parameters (%CD63+ and %CD203chigh) were found between the controls and patients. However, comparisons for %CD63+, %CD203chigh, AUC, and CD-Sens showed similar levels among patients with different symptoms. An optimal cut-off was established from ROC curves, showing a significant positive percentage of BAT in patients compared to controls and great values of sensitivity (>87.5%) and specificity (>85%). In addition, BAT showed differences in LTP-allergic patients tolerant to peanut using its corresponding LTP, Ara h 9. BAT can be used as a potential diagnostic tool for identifying LTP allergy and for differentiating peanut tolerance, although neither reactivity nor sensitivity can distinguish the severity of the clinical symptoms.

Особенности сенсибилизации к молочным белкам у здоровых детей раннего возраста, проживающих в разных мегаполисах РФ

There is no clear answer so far, why, under normal conditions, there is no active immune response to food antigens that are supplied daily with food, while oral tolerance develops in a child. A cohort study of 259 healthy children of the first half year of life who lived in different megalopolises of the Russian Federation showed a high frequency of latent (asymptomatic) sensitization (LS) to milk proteins, which was formed under breast feeding. Despite the transfer to bottle feeding, there was a statistically significant decrease in the frequency of LS to cow and goat milk proteins in babies from Moscow by 5 months of age, and in babies from St. Petersburg by 6 months of age. The frequency of LS to casein, β-LG and α-LA in breastfed babies from Vladivostok during the first three months of life was statistically significantly higher than in babies from Kazan and Khabarovsk during the entire observation period. The data obtained indicate that the immune mechanisms forming latent (asymptomatic) sensitization in the observed children were of an indirect nature, and their implementation was a response to the exposure of maternal allergens that entered the baby’s body in the antenatal and postnatal periods.

Allergen Specificity in Specific IgE Cutoff

To assess the clinical relevance of specific immunoglobulin E (IgE) cutoffs for aeroallergens in children.The population studied includes 6-year-old Danish children in the Copenhagen Prospective Study on Asthma in Childhood in 2000 and 2010.The distribution of 5 common aeroallergens (house dust mite [HDM], cat, dog, grass, and birch) were assessed among children in these cohorts at 6 years old. Levels were compared between the entire population studied and children with pediatrician-diagnosed allergic rhinitis.The median value of specific immunoglobulin E (sIgE) in children varied across groups; all children had a median sIgE of 0.14 (HDM), 0.06 (cat), 0.07 (dog), 0.33 (grass), and 0.2 (birch) kUA/L; symptomatic children with rhinitis had a sIgE of 6.29 (HDM), 1.41 (cat), 5.73 (dog), 2.43 (grass), and 1.97 (birch) kUA/L. In symptomatic children, the median values were higher and had increased variation. There was significant overlap between the 2 sets, with high IgE levels even in some of the asymptomatic children.A uniform cutoff was not found among the allergens tested that discriminate between symptomatic and asymptomatic individuals.Currently, there are no established cutoffs for allergen specific IgE levels that distinguish clinical allergy from asymptomatic sensitization. Having clinically relevant cutoffs for specific IgE levels that correlate with clinical symptoms would facilitate interpretation of test results. The authors’ comparison of allergen specific IgE levels in a prospective cohort of children with a subgroup that had pediatrician-diagnosed allergic rhinitis reveals that there is important overlap of IgE levels between the 2 groups. Similar to food and venom allergy, having detectable IgE has not equate to clinical allergy. In this prospective asthma study, Schoos et al should consider the role of a diagnosis of asthma on the clinical relevance of the sensitization noted, when appropriate to make correlations. Further studies will be needed to determine if allergen specific cutoffs can be established for the diagnosis of rhinitis and asthma.

IgE and IgG4 Repertoire in Asymptomatic HDM-Sensitized and HDM-Induced Allergic Rhinitis Patients

Introduction: Asymptomatic sensitization is defined as the presence of positive skin prick test (SPT) and/or positive serum allergen-specific IgE in the absence of clinical allergic symptoms. Currently, there is no convincing explanation why some people with positive allergen tests do not show symptoms. We aimed to investigate the house dust mite (HDM)-specific IgE and IgG4 repertoire in asymptomatic HDM-sensitized subjects and HDM-induced allergic rhinitis (AR) patients. Methods: A total of 48 subjects sensitized to HDM were included in this study: 27 had AR with/without asthma (symptomatic group), and 21 had no allergic symptoms (asymptomatic group). Six healthy individuals served as control group. Peripheral blood samples were collected for serum IgE and IgG4 assay and basophil activation tests (BATs). IgE and IgG4 assay included antibodies to Dermatophagoides (Der) p1, 2, 7, 10, 21, 23, and Der f1, 2. Results: AR patients had a larger wheal diameter of SPT (7.0 vs. 3.0 mm, p < 0.0001) and a higher specific IgE to Der p (15.50 vs. 0.70 KU/L, p < 0.0001) than asymptomatic subjects. They also showed more frequent sensitization to Der p1 and Der p2 (both p < 0.05). However, the total IgE and specific IgG4 did not differ significantly between the 2 groups. The basophil activation response after being stimulated with HDM was observed to be higher in AR patients (all p < 0.05). Conclusions: There are differences in SPT, serum-specific IgE to Der p, component allergen Der p1 and Der p2 level and BAT between AR patients and asymptomatic subjects sensitized to HDM. IgG4 alone cannot differentiate asymptomatic individuals from AR patients.

Clinical characteristics of asymptomatic allergen sensitization with nasal septal deviation, often misdiagnosed as allergic rhinitis.

Allergic rhinitis (AR) is often defined based on symptoms accompanied by a positive allergen sensitivity test result. However, a positive skin prick test (SPT) does not always imply the occurrence of clinical symptoms. If an asymptomatic allergen-sensitized patient has nasal septal deviation (DSN) that could cause nasal obstruction, the condition could easily be confused with typical symptomatic AR. This study investigated the clinical and laboratory characteristics of asymptomatic allergen-sensitization with septal deviation (ASSD). Patients from a nationwide AR cohort study, conducted in 8 university hospitals, were investigated. AR was diagnosed when there were at least 1 rhinitis symptom with a positive SPT result. The ASSD group included patients who had severe nasal obstruction with few other symptoms and a positive SPT, along with septal deviation. Clinical and laboratory characteristics were compared between the ASSD group and the true AR group. In total, 728 patients were included. The average age was 32.2 ± 12.7 and 66% of the patients had DSN. SPT indicated that ASSD patients were less sensitized to house dust mite (p = 0.019 for Dp and p = 0.021 for Df). There was a significant sex difference: the male-to-female ratio was higher in the ASSD than in the AR group (3.59 vs. 1.77, p = 0.012). However, no statistically significant differences in age, family history, and body mass index were found. ASSD can mimic AR. When dealing with allergen-sensitized patients with a predominant symptom of nasal obstruction, DSN might also be considered before confirming a diagnosis of AR.

Food Reintroduction after Passing an Oral Food Challenge: A Cross-Sectional Structured Interview-Based Assessment of Barriers, Challenges, and Impact on Quality of Life

Asymptomatic sensitization and equivocal history often results in long periods of avoidance. In the case of a negative OFC (OFCneg), the patient must reintroduce the previously avoided food on a regular basis. This population allows for the evaluation of the impact of food allergy delabelling and investigation of challenges linked to food introduction.

Precision Medicine in Hymenoptera Venom Allergy: Diagnostics, Biomarkers, and Therapy of Different Endotypes and Phenotypes.

Allergic reactions to stings of Hymenoptera species may be severe and are potentially fatal deviations of the immunological response observed in healthy individuals. However, venom-specific immunotherapy (VIT) is an immunomodulatory approach able to cure venom allergy in the majority of affected patients. An appropriate therapeutic intervention and the efficacy of VIT not only depend on a conclusive diagnosis, but might also be influenced by the patient-specific manifestation of the disease. As with other diseases, it should be borne in mind that there are different endotypes and phenotypes of venom allergy, each of which require a patient-tailored disease management and treatment scheme. Reviewed here are different endotypes of sting reactions such as IgE-mediated allergy, asymptomatic sensitization or a simultaneous presence of venom allergy and mast cell disorders including particular considerations for diagnosis and therapy. Additionally, phenotypical manifestations of venom allergy, as e.g. differences in age of onset and disease severity, multiple sensitization or patients unsusceptible to therapy, are described. Moreover, biomarkers and diagnostic strategies that might reflect the immunological status of the patient and their value for therapeutic guidance are discussed. Taken together, the increasing knowledge of different disease manifestations in venom hypersensitivity and the growing availability of diagnostic tools open new options for the classification of venom allergy and, hence, for personalized medical approaches and precision medicine in Hymenoptera venom allergy.

Alpha-gal syndrome: challenges to understanding sensitization and clinical reactions to alpha-gal

ABSTRACT Introduction The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody response against the carbohydrate Galα1-3Galβ1-4GlcNAc-R (α-Gal). Tick bites are recognized as the most important cause of anti-α-Gal IgE antibody increase in humans. Several risk factors have been associated with the development of AGS, but their integration into a standardized disease diagnosis has proven challenging. Areas covered Herein we discuss the current AGS diagnosis based on anti-α-Gal IgE titers and propose an algorithm that considers all co-factors in the clinical history of α-Gal-sensitized patients to be incorporated into the AGS diagnosis. The need for identification of host-derived gene markers and tick-derived proteins for the diagnosis of the AGS is also discussed. Expert opinion The current AGS diagnosis based on anti-α-Gal IgE titers has limitations because not all patients sensitized to α-Gal and with anti-α-Gal IgE antibodies higher than the cutoff (0.35 IU/ml) develop anaphylaxis to mammalian meat and AGS. The basophil activation test proposed to differentiate between patients with AGS and asymptomatic α-Gal sensitization cannot be easily implemented as a generalized clinical test. In coming years, the algorithm proposed here could be used in a mobile application for easier AGS diagnosis in the clinical practice.

Atopic dermatitis and its relation to food allergy.

To present the most recent evidence on atopic dermatitis and its relation to food allergy. Atopic dermatitis is a chronic inflammatory disorder of the skin characterized by impaired skin barrier because of multifactorial causes including genetic factors, immune dysregulation, and skin microbiome dysbiosis. Infants with temporary skin barrier disruption and/or persistent atopic dermatitis are particularly at risk of developing food allergy (during the so-called atopic march), with up to half of patients demonstrating positive food-specific IgE and one-third of severe cases of atopic dermatitis having positive symptoms on oral food challenge. A high proportion of children with atopic dermatitis exhibit asymptomatic sensitization to foods, and skin testing to identify potential food triggers is not recommended unless the patient has a history suggestive of food allergy and/or moderate-to-severe atopic dermatitis unresponsive to optimal topical care. Indeed, indiscriminate testing can lead to a high proportion of false-positive tests and harmful dietary evictions. Promising strategies to prevent food allergy in children with atopic dermatitis include early skincare with emollients and treatment with topical steroid, and early introduction of highly allergenic foods. Further studies are required to identify risk factors for atopic dermatitis to help prevent the development of food allergy in this high-risk population.

CyTOF-based Whole Blood Assay to Explore the Allergen Specific Signaling Pathways in Basophil

Peanut allergy is the most common cause of anaphylaxis in childhood. This IgE-mediated allergic reaction is initiated by basophils or mast cells upon exposure and cross-linking of membrane bound IgE by allergens. The subtle molecular and cellular mechanisms that define the difference between peanut allergy and asymptomatic sensitization and during oral immunotherapy are not fully understood. We established a mass cytometry (CyTOF) panel to study differences in allergen specific signaling pathways upon peanut stimulation in human whole blood. In an initial pilot peanut-allergic (n=9) and peanut-sensitized non-allergic children (n=3) were recruited. Fresh blood samples were stimulated with 10pg/ml-100 ng peanut extract, PMA/Ino, anti-FceRI or media control for 3 or 15 minutes. Barcoded samples were pooled and stained with a panel of surface markers and anti-phosphorylation antibodies for p38, erk, mTOR and akt. The samples were acquired on a CyTOF2 and analysis were performed using Cytobank. Positive peanut specific IgE ( 0.30 kUa/L) was detected in peanut-allergic patients but negative sIgE in peanut-sensitized nonallergic. Basophils from peanut-allergic patients showed higher phosphorylation of erk and p38 in dosage-depended manner at 3 minutes whereas phosphorylation of akt and mTOR significantly increased at 15 minutes. Phosphorylation was significantly lower to absent in the sensitized non-allergic patients. We applied the phospho-CyTOF to address the signaling profile after peanut stimulation. This application may allow interesting insights in the kinetics of desensitization during oral immunotherapy.

Asymptomatic toddlers with house dust mite sensitization at risk of asthma and abnormal lung functions at age 7 years

ObjectiveTo evaluate the predictive value of asymptomatic early house dust mite sensitization on allergic outcomes and pulmonary functions in 7-year olds. Study designThe Prediction of Allergies in Taiwanese Children (PATCH) birth cohort study recruited healthy newborns at birth. At age 1.5–2 years, a Dermatophagoides pteronyssinus-specific immunoglobulin E level ≥ 0.35 kU/L was defined as early sensitization. At age 7 years, allergic outcomes were evaluated by pediatric allergists and pulmonologists, and fractional exhaled nitric oxide and pulmonary functions were measured. ResultsAt age 1.5–2 years, 28.0% of toddlers were sensitized to D. pteronyssinus. Among them, 68.2% had no allergic symptoms at that time. At age 7 years, the children with early sensitization had higher risks of asthma (OR = 13.4, 95% CI, 1.2 to 153.0; P = 0.037), allergic rhinitis (OR = 10.2, 95% CI, 2.1 to 49.6; P = 0.004), and atopic dermatitis (OR = 38.5, 95% CI, 2.1 to 696.4; P = 0.014). Notably, even the asymptomatic toddlers with early D. pteronyssinus sensitization had higher probabilities of asthma (12.5% vs. 1.7%, P = 0.040), allergic rhinitis (83.3% vs. 43.1%, P = 0.009), and atopic dermatitis (20.8% vs. 0.0%, P < 0.001) at age 7 years. The asymptomatic toddlers with early sensitization also had higher exhaled nitric oxide levels and higher prevalence of airway hyperresponsiveness at age 7 years. ConclusionAsymptomatic toddlers with early house dust mite sensitization have higher risks of developing asthma, allergic rhinitis, atopic dermatitis, and abnormal lung functions at age 7 years.