Search

Background: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.Methods: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.Findings: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.Interpretation: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.Funding: National Institute of Allergy and Infectious Disease, Immune Tolerance Network. [ABSTRACT FROM AUTHOR]

The article discusses the clinical case that highlights the global health problem in food allergy. It presents evidence-based medicine that support various strategies and formal guidelines on asthma prevalence and prevention. The authors recommend clinical interventions and access to epinephrine autoinjectors and other risk factors like exercise, viral infections, and emotional stress.

The β2-AR (β2-adrenergic receptor) is an important target for respiratory and CVD (cardiovascular disease) medications. Clinical studies suggest that N-terminal polymorphisms of β2-AR may act as disease modifiers. We hypothesized that polymorphisms at amino acids 16 and 27 result in differential trafficking and down-regulation of β2-AR variants following β-agonist exposure. The functional consequences of the four possible combinations of these polymorphisms in the human β2-AR (designated β2-AR-RE, β2-AR-GE, β2-AR-RQ and β2-AR-GQ) were studied using site-directed mutagenesis and recombinant expression in HEK-293 cells (human embryonic kidney cells). Ligand-binding assays demonstrated that after 24 h exposure to 1 μM isoprenaline, isoforms with Arg16 (β2-AR-RE and β2-AR-RQ) underwent increased down-regulation compared with isoforms with Gly16 (β2-AR-GE and β2-AR-GQ). Consistent with these differences in down-regulation between isoforms, prolonged isoprenaline treatment resulted in diminished cAMP response to subsequent isoprenaline challenge in β2-AR-RE relative to β2-AR-GE. Confocal microscopy revealed that the receptor isoforms had similar co-localization with the early endosomal marker EEA1 following isoprenaline treatment, suggesting that they had similar patterns of internalization. None of the isoforms exhibited significant co-localization with the recycling endosome marker Rab11 in response to isoprenaline treatment. Furthermore, we found that prolonged isoprenaline treatment led to a higher degree of co-localization of β2-AR-RE with the lysosomal marker LAMP1 (lysosome-associated membrane protein 1) compared with that of β2-AR-GE. Taken together, these results indicate that a mechanism responsible for differential responses of these receptor isoforms to the β-agonist involves differences in the efficiency with which agonist-activated receptors are trafficked to the lysosomes for degradation, or differences in degradation in the lysosomes. [ABSTRACT FROM AUTHOR]

Background: For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy. Methods: In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months. Results: After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months. Conclusions: These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.) [ABSTRACT FROM PUBLISHER]

Data from many studies have suggested a rise in the prevalence of food allergies during the past 10 to 20 years. Currently, no curative treatments for food allergy exist, and there are no effective means of preventing the disease. Management of food allergy involves strict avoidance of the allergen in the patient's diet and treatment of symptoms as they arise. Because diagnosis and management of the disease can vary between clinical practice settings, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored development of clinical guidelines for the diagnosis and management of food allergy. The guidelines establish consensus and consistency in definitions, diagnostic criteria, and management practices. They also provide concise recommendations on how to diagnose and manage food allergy and treat acute food allergy reactions. The original guidelines encompass practices relevant to patients of all ages, but food allergy presents unique and specific concerns for infants, children, and teenagers. To focus on those concerns, we describe here the guidelines most pertinent to the pediatric population. [ABSTRACT FROM AUTHOR]

The ability to successfully intubate the trachea of rats repeatedly over time, recover them, and perform repeated measures of changes in respiratory mechanics is important. The authors performed experiments utilizing 2 groups of rats at various ages in their development. Rats in the single-measurement group were studied at 1 age only. Rats in the repeated-measurement group were studied at each age point over time. Measurements of respiratory mechanics were made utilizing a forced-oscillation technique. We found no differences in respiratory mechanics between the 2 groups. Our results demonstrate that developing rats can be studied longitudinally to illustrate maturational changes in respiratory mechanics. [ABSTRACT FROM AUTHOR]

Asthma is a disease characterized by reversible airway obstruction. An additional hallmark of chronic asthma is altered wound healing that leads to airway remodeling. Although β-agonists are effective in treating the bronchospasm associated with asthma, their effects on airway wound healing, which are related to airway remodeling, are unknown. It has been demonstrated that β-agonists can alter the signaling of epidermal growth factor (EGF) receptors, which are important in timely wound healing. Therefore, we hypothesized that the β-agonist isoproterenol would affect wound healing. Using an in vitro scrape wound assay, we demonstrated that isoproterenol attenuates EGF-stimulated wound healing in 16HBE airway epithelial cell cultures. Through experiments with forskolin and cells overexpressing β2-adrenergic receptor-yellow fluorescent protein, we show that attenuation is due to the accumulation of cAMP and the involvement of at least one additional pathway. Furthermore, attenuation is not due to a direct effect on the EGF receptor or to an alteration of the ERK/MAPK signaling cascade. Based on these results, we propose that isoproterenol may exert its effects through other MAPK signaling pathways (JNK and/or p38) or through parallel mechanisms. These results also demonstrate a problem of potential therapeutic relevance in which a commonly prescribed medication may alter wound healing and contribute to the remodeling of asthmatic airways. [ABSTRACT FROM AUTHOR]

Asthma morbidity and mortality have increased at alarming rates. Morbidity is significantly higher among minorities and low-income populations. The purpose of this study was to survey pharmacies licensed to provide both asthma medications and durable medical equipment (DME) to evaluate their acceptance of Medicaid as payment for spacers and peak flow meters in patients with Medicaid. Twenty-four pharmacies were identified and completed a telephone survey. Only 64% of the pharmacies licensed to accept Medicaid for DME provide this service. We postulate that improving DME licensing and claims reimbursement will impact medication compliance, as well as asthma morbidity and mortality. [ABSTRACT FROM AUTHOR]

On binding to its receptor, epidermal growth factor (EGF) initiates a cascade of events leading to cell proliferation or differentiation. In addition, the EGF receptor itself is downregulated to attenuate mitogenic signaling. Downregulation occurs through trafficking of receptors to lysosomes, culminating in proteolytic destruction of both the receptor and ligand; however, endocytic sorting mechanisms that underlie lysosomal targeting remain obscure. The goal of this study was to explore one aspect of the molecular basis for ligandinduced lysosomal targeting and degradation of EGF receptors. In this study, we identify a tyrosine-leucine motif (954YLVI) that is essential for transit of ligand-receptor complexes to lysosomes. When this motif is mutated, HEK 293 cells expressing the mutant receptors demonstrate impaired lysosomal targeting and downregulation compared with wildtype receptors. 954YLVI is highly conserved among EGF receptors from various mammalian and invertebrate species and is critical for receptor downregulation. We propose that 954YLVI works in concert with at least two additional regions within the EGF receptor cytoplasmic domain that are essential for efficiently targeting ligand-receptor complexes to the lysosome. [ABSTRACT FROM AUTHOR]

The article presents a study that assessed individualized therapy for persistent asthma in children. Topics discussed include results which show that daily inhaled corticosteroids conferred the most protection against symptoms and exacerbations in children with type 2 inflammation and comments on the study.

The article presents a study that defined the relationships among specific viral illnesses and the type and timing of aeroallergen sensitization with the persistence of asthma into adolescence. Topics discussed include results which show that high-risk children with a parental history of allergies and/or asthma were more likely to develop asthma when they had rhinovirus and aeroallergen sensitization in early childhood and comments on the study.

The article presents a study that evaluated the efficacy, safety, and feasibility of early oral immunotherapy (E-OIT) for treatment of peanut-allergic children. Topics discussed include the effectiveness of early oral immunotherapy with peanut protein at both high- and low-maintenance dosing for inducing sustained unresponsiveness and accelerating the introduction of peanut in the diet of preschool, peanut-allergic children and a review of the study.

The article discusses research on the impact of environmental peanut exposure to peanut sensitization and allergy, in which discussions include increased peanut sensitization and allergy among children exposed to peanut antigen and the need for further research to delineate risks versus benefits of different routes of exposure.

The article discusses research on the impact of infant consumption of processed and raw cow's milk on common infections and fever, in which the value of unprocessed milk on preventing common childhood respiratory illnesses and fever is highlighted.

An abstract of the article "Parental Psychological Distress During Pregnancy and Wheezing in Preschool Children: The Generation R Study" by M. Guxens, A. M. Sonnenschein-van der Voort, and H. Tiemeier is presented.

Epidemiologic studies have demonstrated an association between acetaminophen (APAP) use and the development of asthma symptoms. However, few studies have examined relationships between APAP-induced signaling pathways associated with the development of asthma symptoms. We tested the hypothesis that acute APAP exposure causes airway hyper-responsiveness (AHR) in human airways. Precision cut lung slice (PCLS) airways from humans and mice were used to determine the effects of APAP on airway bronchoconstriction and bronchodilation and to assess APAP metabolism in lungs. APAP did not promote AHR in normal or asthmatic human airways ex vivo. Rather, high concentrations mildly bronchodilated airways pre-constricted with carbachol (CCh), histamine (His), or immunoglobulin E (IgE) cross-linking. Further, the addition of APAP prior to bronchoconstrictors protected the airways from constriction. Similarly, in vivo treatment of mice with APAP (200 mg/kg IP) resulted in reduced bronchoconstrictor responses in PCLS airways ex vivo. Finally, in both mouse and human PCLS airways, exposure to APAP generated only low amounts of APAP-protein adducts, indicating minimal drug metabolic activity in the tissues. These findings indicate that acute exposure to APAP does not initiate AHR, that high-dose APAP is protective against bronchoconstriction, and that APAP is a mild bronchodilator. [ABSTRACT FROM AUTHOR]

An abstract for the article "Adherence to Inhaled Corticosteroids: An Ancillary Study of the Childhood Asthma Management Program Clinical Trial" by J. A. Krishnan and colleagues, is presented.

An abstract of the article "Natural Course and Comorbidities of Allergic and Nonallergic Rhinitis in Children," by M. Westman, P. Stjärne, and A. Asarnoj, is presented.

The article presents a research study involving a comparison of the cost-effectiveness between fluticasone and montelukast in children with mild to moderate persistent asthma. It notes that the findings of the study reveal that fluticasone is more effective in patients who are exhibiting more airway inflammation and are more responsive to methacholine compared with montelukast. It is also affordable which makes fluticasone the preferred asthma controller.

An abstract of the article "Episodic Use of an Inhaled Corticosteroid or Leukotriene Receptor Antagonist in Preschool Children With Moderate-To-Severe Intermittent Wheezing," by L. B. Bacharier, B. R. Phillips and R. S. Zeiger is presented.

The article discusses research on the contribution of environmental exposures on sensitization and food allergy among inner-city children, in which discussions include the impact of longitudinal exposures in an urban setting and modifiable factors associated with the development of food allergy.

An abstract of the article "The Natural History of Egg Allergy," by J.H. Savage and colleagues are presented.

The article discusses research on the efficacy and safety of sublingual immunotherapy (SLIT) in seasonal allergic rhinoconjunctivitis using timothy-grass-allergen tablets. It references a study by S. R. Durham and colleagues in a 2006 issue of the "Journal of Allergy and Clinical Immunology." A double-blind, randomized, parallel-group, placebo-controlled trial was conducted. The findings revealed that grass-pollen SLIT has a dose-dependent efficacy, is well tolerated, and provides improved quality of life (QoL) for patients with seasonal allergic rhinoconjunctivitis.

The article discusses research being done on asthma control test (ACT). It references a study by M. Schatz and colleagues in a 2006 issue of the "Journal of Allergy and Clinical Immunology." The study aims to evaluate the validity and reliability of ACT and assess its responsiveness to changes in asthma control over time in patients who were new to the care of an asthma specialist. An overview of the study population is presented, as well as the methods, findings and conclusions. Reviewer comments are included.

Presents an abstract of the study 'Insect Sting Allergy With Negative Venom Skin Test Responses,' by D.B.K. Golden, A. Kagey-Sobotka, P.S. Norman, R.G. Hamilton and L.M. Lichtenstein, from a 2001 issue of the 'Journal of Allergy and Clinical Immunology.'

Presents an abstract of the study 'A Voluntary Registry for Peanut and Tree Nut Allergy: Characteristics of the First 5149 Registrants,' by S.H. Sicherer, T.J. Furlong, A. Munoz-Furlong, A.W. Burks, H.A. Sampson, from a 2001 issue of the 'Journal of Allergy and Clinical Immunology.'

Presents an abstract of the study `Evidence for a Disease-Promoting Effect of Staphylococcus Aureus-Derived Exotoxins in Atopic Dermatitis,' by R. Bunikowski, M.E.A. Mielke and H. Skarabis, published in a 2000 issue of the `Journal of Allergy and Clinical Immunology.'

An abstract of the article "Sustained Unresponsiveness to Peanut in Subjects Who Have Completed Peanut Oral Immunotherapy" by B. P. Vickery, A. M. Scurlock, and M. Kulis is presented.

An abstract of the article "The Natural History and Clinical Predictors of Egg Allergy in the First 2 Years of Life: A Prospective, Population-Based Cohort Study" by R. L. Peters, S. C. Dharmage, and L. C. Gurrin is presented.

Presents information on a study which developed a questionnaire to measure the quality of life in children with seasonal allergic rhinoconjunctivitis. Methodology; Results; Conclusions.

Type 2 allergen‐specific T cells are essential for the induction and maintenance of allergies to foods, and Tregs specific for these allergens are assumed to be involved in their resolution. However, it has not been convincingly demonstrated whether allergen‐specific Treg responses are responsible for the generation of oral tolerance in humans. We observed that sustained food allergen exposure in the form of oral immunotherapy resulted in increased frequency of Tregs only in individuals with lasting clinical tolerance. We sought to identify regulatory components of the CD4+ T‐cell response to food allergens by studying their functional activation over time in vitro and in vivo. Two subsets of Tregs expressing CD137 or CD25/OX40 were identified with a delayed kinetics of activation compared with clonally enriched pathogenic effector Th2 cells. Treg activation was dependent on IL‐2 derived from effector T cells. In vivo exposure to peanut in the form of an oral food challenge of allergic subjects induced a delayed and persistent activation of Tregs after initiation of the allergen‐specific Th2 response. The novel finding of our work is that a sustained wave of Treg activation is induced by the release of IL‐2 from Th2 effector cells, with the implication that therapeutic administration of IL‐2 could improve current OIT approaches. [ABSTRACT FROM AUTHOR]

The article reports on the study which has investigated the application of timothy grass allergen immunotherapy (AIT) on youth with grass pollen-induced allergic rhinoconjunctivitis (ARC) in North America. It notes that anticipated and acceptable adverse effects are featured in the treatment of ARC through AIT. It mentions that quality of life has improved at the peak of the allergy season.

The article presents a research study which determines the connection between allergic rhinitis (AR) and wheezing cough in school-age children. Study shows the variation of acquiring wheezing cough in these children due to different stratification age and phenotypes of the said rhinitis. However, it cites the association of the two diseases in preschool children. Moreover, the benefits of this study for the early treatment of children is also reported.

An abstract of the article "Efficacy and Safety of 5-Grass-Pollen Sublingual Immunotherapy Tablets in Pediatric Allergic Rhinoconjunctivitis," by U. Wahn, A. Tabar and P. Kuna is presented.

An abstract of the article "A Randomized, Double-Blind, Placebo-Controlled Study of Milk Oral Immunotherapy for Cow's Milk Allergy," by J. Skripak, S. Nash and H. Rowley is presented.

An abstract of the article "Effect of Different Antiasthmatic Treatments on Exercise-Induced Bronchoconstriction in Children With Asthma," by I. Stelmach and colleagues is presented.

An abstract of the article "Specific Verbal Tolerance Induction in Children With Very Severe Cow's Milk-Induced Reactions," by G. Longo and colleagues is presented.

The article discusses research being done on the use of skin-prick tests (SPT) to determine children with low egg white-specific immunoglobulin E (IgE) levels. It references a study by A. K. Knight and colleagues published in a 2006 issue of the "Journal of Allergy & Clinical Immunology." This study was a retrospective analysis of oral egg challenges in children with egg allergy and low egg white-specific IgE antibody levels. Key findings found that egg-allergic children with low egg-white-specific IgE levels, a small SPT response and a low egg/histamine index are more likely to pass oral food challenges.

Presents an abstract of the study 'Association of Specific Allergen Sensitization With Socioeconomic Factors and Allergic Disease in a Population of Boston Women,' by S.A. Lewis, S.T. Weiss, T.A.E. Platts-Mills, B.A. Syrin and D.R. Gold, from a 2001 issue of the 'Journal of Allergy and Clinical Immunology.'

Presents an abstract of the study `Comparison of Once- and Twice-Daily Dosing of Fluticasone Propionate 200 Micrograms Per Day Administered by Diskus Device in Patients With Asthma Treated With or Without Inhaled Cortisteroids,' by J. Wolfe, A. Rooklin, J. Grady and colleages, published in a 2000 issue of the `Journal of Allergy and Clinical Immunology.'

Presents an abstract of the study `A Murine Model of Peanut Anaphylaxis: T- and B-cell Responses to a Major Peanut Allergen Mimic Human Responses,' by X-M. Li, D. Serebrisky, S-Y. Lee and colleagues, published in a 2000 issue of the `Journal of Allergy and Clinical Immunology.'

Presents information on a study which discussed the clinical characteristics of steroid-insensitive asthma in response to oral glucocorticoids in adolescent asthmatics. Methods; Results; Conclusions.

Studies the clinical pharmacology of epinephrine in allergic children with a history of anaphylaxis. Experimental procedures; Results; Conclusions.

Background: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder‐dnfp (PTAH)—formerly AR101—has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy‐related quality of life. Methods: We present a subset analysis of PALISADE‐ARC004 participants (aged 4–17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double‐blind, placebo‐controlled food challenge (DBPCFC); skin prick testing; peanut‐specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores. Results: Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose‐limiting symptoms. Immune biomarkers showed a pattern consistent with treatment‐induced desensitization. Among PTAH‐continuing participants, the overall and treatment‐related exposure‐adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life. Conclusions: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response. [ABSTRACT FROM AUTHOR]

Introduction: Molecular studies of hen's egg allergens help define allergic phenotypes, with IgE to sequential (linear) epitopes on the ovomucoid (OVM) protein associated with a persistent disease. Epitope profiles of other egg allergens are largely unknown. The objective of this study was to construct an epitope library spanning across 7 allergens and further evaluate sequential epitope-specific (ses-)IgE and ses-IgG4 among baked-egg reactive or tolerant children. Methods: A Bead-Based Epitope Assay was used to identify informative IgE epitopes from 15-mer overlapping peptides covering the entire OVM and ovalbumin (OVA) proteins in 38 egg allergic children. An amalgamation of 12 B-cell epitope prediction tools was developed using experimentally identified epitopes. This ensemble was used to predict epitopes from ovotransferrin, lysozyme, serum albumin, vitellogenin-II fragment, and vitellogenin-1 precursor. Ses-IgE and ses-IgG4 repertoires of 135 egg allergic children (82 reactive to baked-egg, the remaining 52 tolerant), 46 atopic controls, and 11 healthy subjects were compared. Results: 183 peptides from OVM and OVA were screened and used to create an aggregate algorithm, improving predictions of 12 individual tools. A final library of 65 sequential epitopes from 7 proteins was constructed. Egg allergic children had higher ses-IgE and lower ses-IgG4 to predominantly OVM epitopes than both atopic and healthy controls. Baked-egg reactive children had similar ses-IgG4 but greater ses-IgE than tolerant group. A combination of OVA-sIgE with ses-IgEs to OVM-023 and OVA-028 was the best predictor of reactive phenotype. Conclusion: We have created a comprehensive epitope library and showed that ses-IgE is a potential biomarker of baked-egg reactivity. [ABSTRACT FROM AUTHOR]

Background: The β2-adrenergic receptor (β2AR) is a primary target for medications used to treat asthma. Due to the low abundance of β2AR, very few studies have reported its localization in tissues. However, the intracellular location of β2AR in lung tissue, especially in airway smooth muscle cells, is very likely to have a significant impact on how the airways respond to β-agonist medications. Thus, a method for visualizing β2AR in tissues would be of utility. The purpose of this study was to develop an immunofluorescent labeling technique for localizing native and recombinant β2AR in primary cell cultures. Methods: A panel of six different antibodies were evaluated in indirect immunofluorescence assays for their ability to recognize human and rat β2AR expressed in HEK 293 cells. Antibodies capable of recognizing rat β2AR were identified and used to localize native β2AR in primary cultures of rat airway smooth muscle and epithelial cells. β2AR expression was confirmed by performing ligand binding assays using the β-adrenergic antagonist [3H] dihydroalprenolol ([3H]DHA). Results: Among the six antibodies tested, we identified three of interest. An antibody developed against the C-terminal 15 amino acids of the human β2AR (Ab-Bethyl) specifically recognized human but not rat β2AR. An antibody developed against the C-terminal domain of the mouse β2AR (Ab-sc570) specifically recognized rat but not human β2AR. An antibody developed against 78 amino acids of the C-terminus of the human β2AR (Ab-13989) was capable of recognizing both rat and human β2ARs. In HEK 293 cells, the receptors were predominantly localized to the cell surface. By contrast, about half of the native rat β2AR that we visualized in primary cultures of rat airway epithelial and smooth muscle cells using Ab-sc570 and Ab-13989 was found inside cells rather than on their surface. Conclusion: Antibodies have been identified that recognize human β2AR, rat β2AR or both rat and human β2AR. Interestingly, the pattern of expression in transfected cells expressing millions of receptors was dramatically different from that in primary cell cultures expressing only a few thousand native receptors. We anticipate that these antibodies will provide a valuable tool for evaluating the expression and trafficking of β2AR in tissues. [ABSTRACT FROM AUTHOR]

Background: Prognostication of peanut allergy (PNA) is relevant for early interventions. We aimed to determine baseline parameters associated with the development of PNA in 3‐ to 15‐month‐olds with likely egg and/or milk allergy, and/or moderate to severe atopic dermatitis (AD) and a positive egg/milk skin prick test (SPT), but no known PNA. Methods: The primary endpoint was PNA [confirmed/convincing diagnosis or last classified as serologic PNA (<2 years, ≥5 kUA/L, otherwise ≥14 kUA/L, peanut IgE)] among 511 participants (median follow‐up, 7.3 years). Associations were explored with univariate logistic regression; factors with P < 0.15 were analyzed by stepwise multiple logistic regression, using data stratified by PNA status and randomly assigned to development and validation datasets. Results: 205/511 (40.1%) had PNA. Univariate factors associated with PNA (P < 0.01) included increased AD severity, larger egg and peanut SPT, greater egg, milk, peanut, Ara h1‐h3 IgE, higher peanut IgG and IgG4, and increased pregnancy peanut consumption. P‐values were between 0.01 and 0.05 for younger age, non‐white race, lack of breastfeeding, and increased lactation peanut consumption. Using a development dataset, the multivariate model identified younger age at enrollment, greater peanut and Ara h2 IgE, and lack of breastfeeding as prognosticators. The final model predicted 79% in the development and 75% in the validation dataset (AUC = 0.83 for both). Models using stricter or less strict PNA criteria both found Ara h2 as predictive. Conclusions: Key factors associated with PNA in this high‐risk population included lack of breastfeeding, age, and greater Ara h2 and peanut‐specific IgE, which can be used to prognosticate outcomes. [ABSTRACT FROM AUTHOR]