Search

[Display omitted] Rising rates of peanut allergy (PA) motivate investigations of its development to inform prevention and therapy. Microbiota and the metabolites they produce shape food allergy risk. We sought to gain insight into gut microbiome and metabolome dynamics in the development of PA. We performed a longitudinal, integrative study of the gut microbiome and metabolome of infants with allergy risk factors but no PA from a multicenter cohort followed through mid-childhood. We performed 16S rRNA sequencing, short chain fatty acid measurements, and global metabolome profiling of fecal samples at infancy and at mid-childhood. In this longitudinal, multicenter sample (n = 122), 28.7% of infants developed PA by mid-childhood (mean age 9 years). Lower infant gut microbiome diversity was associated with PA development (P =.014). Temporal changes in the relative abundance of specific microbiota and gut metabolite levels significantly differed in children who developed PA. PA-bound children had different abundance trajectories of Clostridium sensu stricto 1 sp (false discovery rate (FDR) = 0.015) and Bifidobacterium sp (FDR = 0.033), with butyrate (FDR = 0.045) and isovalerate (FDR = 0.036) decreasing over time. Metabolites associated with PA development clustered within the histidine metabolism pathway. Positive correlations between microbiota, butyrate, and isovalerate and negative correlations with histamine marked the PA-free network. The temporal dynamics of the gut microbiome and metabolome in early childhood are distinct for children who develop PA. These findings inform our thinking on the mechanisms underlying and strategies for potentially preventing PA. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) and food allergy (FA) are strongly associated, with one-third of children with AD developing concomitant FA. Epithelial barrier dysfunction is important in both conditions. Genetic factors, such as filaggrin mutations and IL-4 receptor alpha chain polymorphisms, are linked to increased risk. In addition, several environmental exposures lead to reduced filaggrin and contribute to skin barrier dysfunction. Staphylococcus aureus colonization appears to contribute to AD and FA, as well as activating the type 2 immune response. Comprehensive multiomic studies using skin tape stripping have identified distinct atopic endotypes with unique characteristics of the stratum corneum lipids, proteins, S aureus abundance, and type 2 cytokine expression. Our new understanding of AD and FA presents an area of opportunity to move toward improved diagnosis and prevention of atopy. [ABSTRACT FROM AUTHOR]

[Display omitted] Food allergy (FA) often occurs in early childhood with and without atopic dermatitis (AD). FA can be severe and even fatal. For primary prevention, it is important to find early biomarkers to predict the future onset of FA before any clinical manifestations. Our aim was to find early predictors of future onset of FA in the stratum corneum (SC). Skin tape strips were collected from the forearm of newborns (n = 129) at age 2 months, before any signs of clinical FA or AD. Children were clinically monitored until they reached age 2 years to confirm the presence or absence of FA and AD. Skin tape strips were subjected to lipidomic analyses by liquid chromatography–tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. Overall, 9 of 129 infants (7.0%) developed FA alone and 9 of 129 infants (7.0%) developed FA concomitantly with AD. In the stratum corneum of children with future FA and concomitant AD and FA, absolute amounts of unsaturated (N24:1)(C18-sphingosine)ceramide and (N26:1)(C18-sphingosine)ceramide and their relative percentages within the molecular group were increased compared with the amounts and percentages in healthy children, with P values ranging from less than.01 to less than.05 according to ANOVA. The children with future AD had normal levels of these molecules. IL-33 level was upregulated in those infants with future FA but not in those with future AD, whereas thymic stromal lymphopoietin was upregulated in those with future AD but not in those with future FA. Logistic regression analysis revealed strong FA predicting power for the combination of dysregulated lipids and cytokines, with an odds ratio reaching 101.4 (95% CI = 5.4-1910.6). Noninvasive skin tape strip analysis at age 2 months can identify infants at risk of FA in the future. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) and food allergy (FA) are associated with skin barrier dysfunction. Skin biomarkers are needed for skin barrier interventions studies. In this study, skin tape strip (STS) samples were collected from nonlesional skin of 62 children in AD FA + , AD FA − , and nonatopic groups for mass spectrometry proteomic analysis. transepidermal water loss and allergic sensitization were assessed. STS proteomic analysis results were validated in an independent cohort of 41 adults with AD with and without FA versus nonatopic controls. A group of 45 proteins was identified as a principal component 1 (PC1) with the highest expression in AD FA + STSs. This novel set of STS proteins was highly correlative to skin transepidermal water loss and allergic sensitization. PC1 proteins included keratin intermediate filaments; proteins associated with inflammatory responses (S100 proteins, alarmins, protease inhibitors); and glycolysis and antioxidant defense enzymes. Analysis of PC1 proteins expression in an independent adult AD cohort validated differential expression of STS PC1 proteins in the skin of adult patients with AD with the history of clinical reactions to peanut. STS analysis of nonlesional skin of AD children identified a cluster of proteins with the highest expression in AD FA + children. The differential expression of STS PC1 proteins was confirmed in a replicate cohort of adult AD patients with FA to peanut, suggesting a unique STS proteomic endotype for AD FA+ that persists into adulthood. Collectively, PC1 proteins are associated with abnormalities in skin barrier integrity and may increase the risk of epicutaneous sensitization to food allergens. [ABSTRACT FROM AUTHOR]

Unexpected allergic reactions to peanut are the most common cause of fatal food-related anaphylaxis. Mechanisms underlying the variable severity of peanut-allergic reactions remain unclear. We sought to expand mechanistic understanding of reaction severity in peanut allergy. We performed an integrated transcriptomic and epigenomic study of peanut-allergic children as they reacted in vivo during double-blind, placebo-controlled peanut challenges. We integrated whole-blood transcriptome and CD4+ T-cell epigenome profiles to identify molecular signatures of reaction severity (ie, how severely a peanut-allergic child reacts when exposed to peanut). A threshold-weighted reaction severity score was calculated for each subject based on symptoms experienced during peanut challenge and the eliciting dose. Through linear mixed effects modeling, network construction, and causal mediation analysis, we identified genes, CpGs, and their interactions that mediate reaction severity. Findings were replicated in an independent cohort. We identified 318 genes with changes in expression during the course of reaction associated with reaction severity, and 203 CpG sites with differential DNA methylation associated with reaction severity. After replicating these findings in an independent cohort, we constructed interaction networks with the identified peanut severity genes and CpGs. These analyses and leukocyte deconvolution highlighted neutrophil-mediated immunity. We identified NFKBIA and ARG1 as hubs in the networks and 3 groups of interacting key node CpGs and peanut severity genes encompassing immune response, chemotaxis, and regulation of macroautophagy. In addition, we found that gene expression of PHACTR1 and ZNF121 causally mediates the association between methylation at corresponding CpGs and reaction severity , suggesting that methylation may serve as an anchor upon which gene expression modulates reaction severity. Our findings enhance current mechanistic understanding of the genetic and epigenetic architecture of reaction severity in peanut allergy. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) affects up to 20% of children worldwide and is an increasing public health problem, particularly in developed countries. Although AD in infants and young children can resolve, there is a well-recognized increased risk of sequential progression from AD to other atopic diseases, including food allergy (FA), allergic rhinitis, allergic asthma, and allergic rhinoconjunctivitis, a process referred to as the atopic march. The mechanisms underlying the development of AD and subsequent progression to other atopic comorbidities, particularly FA, are incompletely understood and the subject of intense investigation. Other major research objectives are the development of effective strategies to prevent AD and FA, as well as therapeutic interventions to inhibit the atopic march. In 2017, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop to discuss current understanding and important advances in these research areas and to identify gaps in knowledge and future research directions. International and national experts in the field were joined by representatives from several National Institutes of Health institutes. Summaries of workshop presentations, key conclusions, and recommendations are presented herein. [ABSTRACT FROM AUTHOR]

The Consortium for Food Allergy Research (CoFAR) was established by the National Institute of Allergy and Infectious Diseases in 2005 as a collaborative research program bringing together centers focused on the study of food allergy. CoFAR was charged with developing studies to better understand the pathogenesis and natural history of food allergy, as well as potential approaches to the treatment of food allergy. In its first iteration an observational study of infants with milk and egg allergy was established, and studies of oral immunotherapy for egg allergy and sublingual immunotherapy for peanut allergy were initiated, as was a phase 1 study of a recombinant peanut protein vaccine. CoFAR was renewed in 2010 for an additional 5-year period during which the initial observational study was continued, a study of eosinophilic esophagitis was initiated, and new therapeutic trials were established to study epicutaneous immunotherapy for peanut allergy and to compare the safety and efficacy of egg oral immunotherapy to the ingestion of baked egg for the treatment of egg allergy. The results of these efforts will be reviewed in this rostrum, with a brief look to the future of CoFAR. [ABSTRACT FROM AUTHOR]

Background The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood. Objectives Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of subjects with and without peanut allergy (PA). Methods We obtained samples from patients with PA, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (Consortium of Food Allergy Research [CoFAR] 6). Subjects were confirmed as having PA, or if they passed a 1-g peanut challenge, they were termed high-threshold subjects. Healthy control (HC) subjects were also recruited. Peanut-responsive T cells were identified based on CD154 expression after 6 to 18 hours of stimulation with peanut extract. Cells were analyzed by using flow cytometry and single-cell RNA sequencing. Results Patients with PA had tissue- and follicle-homing peanut-responsive CD4 + T cells with a heterogeneous pattern of T H 2 differentiation, whereas control subjects had undetectable T-cell responses to peanut. The PA group had a delayed and IL-2–dependent upregulation of CD154 on cells expressing regulatory T (Treg) cell markers, which was absent in HC or high-threshold subjects. Depletion of Treg cells enhanced cytokine production in HC subjects and patients with PA in vitro , but cytokines associated with highly differentiated T H 2 cells were more resistant to Treg cell suppression in patients with PA. Analysis of gene expression by means of single-cell RNA sequencing identified T cells with highly correlated expression of IL4 , IL5 , IL9 , IL13 , and the IL-25 receptor IL17RB . Conclusions These results demonstrate the presence of highly differentiated T H 2 cells producing T H 2-associated cytokines with functions beyond IgE class-switching in patients with PA. A multifunctional T H 2 response was more evident than a Treg cell deficit among peanut-responsive T cells. [ABSTRACT FROM AUTHOR]

PRACTALL is a joint initiative of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology to provide shared evidence-based recommendations on cutting-edge topics in the field of allergy and immunology. PRACTALL 2017 is focused on what has been established regarding the role of the microbiome in patients with asthma, atopic dermatitis, and food allergy. This is complemented by outlining important knowledge gaps regarding its role in allergic disease and delineating strategies necessary to fill these gaps. In addition, a review of progress in approaches used to manipulate the microbiome will be addressed, identifying what has and has not worked to serve as a baseline for future directions to intervene in allergic disease development, progression, or both. [ABSTRACT FROM AUTHOR]

Background Gut microbiota may play a role in the natural history of cow's milk allergy. Objective We sought to examine the association between early-life gut microbiota and the resolution of cow's milk allergy. Methods We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Results Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η 2 = 0.43; ANOVA P = .034). Conclusions Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy. [ABSTRACT FROM AUTHOR]

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year. [ABSTRACT FROM AUTHOR]

Background: Peanut allergy is typically severe, lifelong, and prevalent. Objective: To identify factors associated with peanut sensitization. Methods: We evaluated 503 infants 3 to 15 months of age (mean, 9.4 months) with likely milk or egg allergy but no previous diagnosis of peanut allergy. A total of 308 had experienced an immediate allergic reaction to cow''s milk and/or egg, and 204 had moderate to severe atopic dermatitis and a positive allergy test to milk and/or egg. A peanut IgE level ≥5 kUA/L was considered likely indicative of peanut allergy. Results: A total of 140 (27.8%) infants had peanut IgE levels ≥5 kUA/L. Multivariate analysis including clinical, laboratory, and demographic variables showed frequent peanut consumption during pregnancy (odds ratio, 2.9; 95% CI, 1.7-4.9; P < .001), IgE levels to milk (P = .001) and egg (P < .001), male sex (P = .02), and nonwhite race (P = .02) to be the primary factors associated with peanut IgE ≥5 kUA/L. Frequency of peanut consumption during pregnancy and breast-feeding showed a dose-response association with peanut IgE ≥5 kUA/L, but only consumption during pregnancy was a significant predictor. Among 71 infants never breast-fed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE ≥5 kUA/L (odds ratio, 4.99, 95% CI, 1.69-14.74; P < .004). Conclusion: In this cohort of infants with likely milk or egg allergy, maternal ingestion of peanut during pregnancy was strongly associated with a high level of peanut sensitization. [Copyright &y& Elsevier]

This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-α-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. [Copyright &y& Elsevier]

Consortium for Food Allergy Research investigators previously reported 52-week outcomes from a randomized controlled trial of peanut epicutaneous immunotherapy, observing modest and statistically significant induction of desensitization, highest in children ages 4 to 11 years. We sought to evaluate changes in efficacy, safety, and mechanistic parameters following extended open-label peanut epicutaneous immunotherapy. Peanut-allergic participants (4-25 years) received 52 weeks of placebo (PLB), Viaskin Peanut 100 μg (VP100) or 250 μg (VP250), and then crossed over to VP250 for PLB (PLB-VP250) and VP100 (VP100-VP250) participants and continued treatment for VP250 participants (total = 130 weeks of active epicutaneous immunotherapy). Efficacy was assessed by double-blind, placebo-controlled food challenge (5044 mg peanut protein), and adherence, safety, and mechanistic parameters were evaluated. At week 130, desensitization success was achieved in 1 of 20 (5%) PLB-VP250, 5 of 24 (20.8%) VP100-VP250, and 9 of 25 (36%) VP250 participants, with median successfully consumed dose change from baseline of 11.5 mg, 141.5 mg, and 400 mg, respectively. Median age (years) for week 130 desensitization success was 6.2 years (interquartile range, 5.2-9.1) versus 9.4 years (interquartile range, 7.6-12.8) for failures (P <.001). Adherence was 96%. Adverse reactions were predominantly local patch-site reactions. Significant increases in peanut- and Ara h2–specific IgG 4 observed at week 52 persisted to week 130. By a post hoc analysis, there were no statistically significant increases from week 52 to week 130 in either desensitization success or successfully consumed dose. Extended treatment with VP250 was well tolerated, and desensitization observed at week 52 persisted between weeks 52 and 130. Treatment success was observed predominantly in younger participants, with younger age at initiation of active therapy an important predictor of success. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including the advances in food allergy, the factors impacting the prevalence of food energy, and the guidelines for the diagnosis of food allergy.

The nonlesional skin of children with atopic dermatitis (AD) with peanut allergy (PA) is associated with increased transepidermal water loss; low urocanic acid (UCA) and pyrrolidone carboxylic acid (PCA), both of which are filaggrin breakdown products; and a reduced ratio of esterified ω-hydroxy fatty acid sphingosine ceramides (EOS-CERs) to nonhydroxy fatty acid sphingosine ceramides (NS-CERs) in the skin. The skin barrier of subjects with PA without AD (AD–PA+) has not been studied. Our aim was to explore whether AD–PA+ is associated with skin barrier abnormalities. A total of 33 participants were enrolled, including 13 AD–PA+, 9 AD+PA+, and 11 nonatopic (NA) participants. The PCA content in the stratum corneum of AD–PA+ subjects was significantly reduced versus that in NA subjects (median level, 67 vs 97 μg/mg protein [ P =.028]). The ratio between cis - and trans -UCA decreased significantly from being highest in the NA group (1.62) to lowest in AD+PA+ group (0.07 [ P <.001 vs in the NA group; P =.006 vs in the AD–PA+ group]), with the AD–PA+ group having an intermediate cis/trans -UCA ratio (1.17 [ P =.024 vs in the NA group]). The TEWL in AD–PA+ subjects did not differ from that in the group with NA skin. Interestingly, AD–PA+ subjects had an increased EOS/NS-CER ratio versus that in the group of subjects with NA skin (1.9 vs 1.3 [ P =.008]), whereas the AD+PA+ group had a decreased proportion of EOS-CERs (0.8 [ P =.001] vs in the AD–PA+ group). Our data demonstrate that irrespective of AD, PA is associated with decreased skin cis-UCA and PCA content. An increase in skin EOS-CER/NS-CER ratio separates the AD–PA+ group from the AD+PA+ and NA groups. [ABSTRACT FROM AUTHOR]

The aims of the Keystone Symposium conference, "Origins of allergic disease: Microbial, epithelial and immune interactions" were to present and discuss potential microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders, as well as immune mechanisms that might suggest novel disease prevention or intervention strategies. Cross-talk and sharing of ideas among participating experts in basic science and clinical aspects of allergic diseases provided substantial insight into the concept of allergic disorders as a systems disease. The overriding message distilled from the discussions was that damage to epithelial surfaces lies at the origin of the various manifestations of allergic disease. The epithelium of the lungs, gut, and skin, which operates as a critical sensor of environmental stimuli, is besieged by an onslaught of contemporary environmental forces including an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. Collectively, this onslaught leads to alterations of lung, skin, or gut epithelial surfaces, driving a type 2 immune response that underlies most, if not all, of the atopic diseases. Possible remedies for treatment and prevention of allergic diseases were discussed, including a precision medicine approach using biologics, oral desensitization, targeted gut microbiome alterations, and behavior alteration. [ABSTRACT FROM AUTHOR]

Background Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment. Objective We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy. Methods In this multicenter, double-blind, randomized, placebo-controlled study, 74 participants with peanut allergy (ages 4-25 years) were treated with placebo (n = 25), Viaskin Peanut 100 μg (VP100; n = 24) or Viaskin Peanut 250 μg (VP250; n = 25; DBV Technologies, Montrouge, France). The primary outcome was treatment success after 52 weeks, which was defined as passing a 5044-mg protein oral food challenge or achieving a 10-fold or greater increase in successfully consumed dose from baseline to week 52. Adverse reactions and mechanistic changes were assessed. Results At week 52, treatment success was achieved in 3 (12%) placebo-treated participants, 11 (46%) VP100 participants, and 12 (48%) VP250 participants ( P = .005 and P = .003, respectively, compared with placebo; VP100 vs VP250, P = .48). Median change in successfully consumed doses were 0, 43, and 130 mg of protein in the placebo, VP100, and VP250 groups, respectively (placebo vs VP100, P = .014; placebo vs VP250, P = .003). Treatment success was higher among younger children ( P = .03; age, 4-11 vs >11 years). Overall, 14.4% of placebo doses and 79.8% of VP100 and VP250 doses resulted in reactions, predominantly local patch-site and mild reactions ( P = .003). Increases in peanut-specific IgG 4 levels and IgG 4 /IgE ratios were observed in peanut EPIT-treated participants, along with trends toward reduced basophil activation and peanut-specific T H 2 cytokines. Conclusions Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children. This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy. [ABSTRACT FROM AUTHOR]

Background We previously reported the results of a randomized placebo-controlled study of egg oral immunotherapy (eOIT) in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report the results of treatment through 4 years and long-term follow-up. Objective We sought to evaluate the efficacy and safety of eOIT in participants treated up to 4 years. Methods Children with egg allergy (5-18 years old) received eOIT (n = 40) for up to 4 years or placebo (n = 15) for 1 year or less. The key outcome was the percentage of subjects achieving SU by year 4. Safety and immunologic assessments were performed, and long-term follow-up questionnaires (LFQs) were administered after study conclusion (LFQ-1) and 1 year later (LFQ-2). Results Of 40 eOIT-treated subjects, 20 (50.0%) of 40 demonstrated SU by year 4. For those subjects still dosing during years 3 and 4, mild symptoms were present in 12 (54.5%) of 22 subjects. At the time of the LFQ, more subjects receiving eOIT (LFQ-1, 23/34 [68%]; LFQ-2, 21/33 [64%]) were consuming unbaked and baked egg versus placebo (LFQ-1, 2/11 [18%], P = .006; LFQ-2, 3/12 [25%], P = .04). Of subjects achieving SU, 18 (90%) of 20 completed the LFQ, with 18 (100%) of 18 reporting consumption of all forms of egg. When compared with subjects not achieving SU, subjects achieving SU had higher IgG 4 values ( P = .001) and lower egg skin prick test scores ( P = .0002) over time and a lower median baseline ratio of egg-specific IgE to total IgE (1.1% vs 2.7%, P = .04). Conclusions SU after eOIT is enhanced with longer duration of therapy and increases the likelihood of tolerating unbaked egg in the diet. [ABSTRACT FROM AUTHOR]

Background: Immune features of infants with food allergy have not been delineated. Objectives: We sought to explore the basic mechanisms responsible for food allergy and identify biomarkers, such as skin prick test (SPT) responses, food-specific IgE levels, and mononuclear cell responses, in a cohort of infants with likely milk/egg allergy at increased risk of peanut allergy. Methods: Infants aged 3 to 15 months were enrolled with a positive SPT response to milk or egg and either a corresponding convincing clinical history of allergy to milk or egg or moderate-to-severe atopic dermatitis. Infants with known peanut allergy were excluded. Results: Overall, 512 infants (67% male) were studied, with 308 (60%) having a history of a clinical reaction. Skin test responses, detectable food-specific IgE, or both revealed sensitization as follows: milk, 78%; egg, 89%; and peanut, 69%. SPT responses and food-specific IgE levels were discrepant for peanut (15% for IgE ≥0.35 kUA/L and negative SPT response vs 8% for positive SPT response and IgE <0.35 kUA/L, P = .001). Mononuclear cell allergen stimulation screening for CD25, cytokine-inducible SH2-containing protein (CISH), forkhead box protein 3 (FOXP3), GATA3, IL10, IL4, IFNG, and T-box transcription factor (TBET) expression by using casein, egg white, and peanut revealed that only allergen-induced IL4 expression was significantly increased in those with clinical allergy to milk (compared with nonallergic subjects) and in those sensitized to peanut, despite the absence of an increase in GATA3 mRNA expression. Conclusions: Infants with likely milk/egg allergy are at considerably high risk of having increased peanut-specific IgE levels (potential allergy). Peanut-specific serum IgE levels were a more sensitive indicator of sensitization than SPT responses. Allergen-specific IL4 expression might be a marker of allergic risk. Absence of an increase in GATA3 mRNA expression suggests that allergen-specific IL-4 might not be of T-cell origin. [Copyright &y& Elsevier]

Background: A subset of subjects with atopic dermatitis (AD) are susceptible to serious infections with herpes simplex virus, called eczema herpeticum, or vaccina virus, called eczema vaccinatum. Objective: This National Institute of Allergy and Infectious Diseases–funded multicenter study was performed to establish a database of clinical information and biologic samples on subjects with AD with and without a history of eczema herpeticum (ADEH+ and ADEH− subjects, respectively) and healthy control subjects. Careful phenotyping of AD subsets might suggest mechanisms responsible for disseminated viral infections and help identify at-risk individuals. Methods: We analyzed the data from 901 subjects (ADEH+ subjects, n = 134; ADEH− subjects, n = 419; healthy control subjects, n = 348) enrolled between May 11, 2006, and September 16, 2008, at 7 US medical centers. Results: ADEH+ subjects had more severe disease based on scoring systems (Eczema Area and Severity Index and Rajka-Langeland score), body surface area affected, and biomarkers (circulating eosinophil counts and serum IgE, thymus and activation-regulated chemokine, and cutaneous T cell–attracting chemokine) than ADEH− subjects (P < .001). ADEH+ subjects were also more likely to have a history of food allergy (69% vs 40%, P < .001) or asthma (64% vs 44%, P < .001) and were more commonly sensitized to many common allergens (P < .001). Cutaneous infections with Staphylococcus aureus or molluscum contagiosum virus were more common in ADEH+ subjects (78% and 8%, respectively) than in ADEH− subjects (29% and 2%, respectively; P < .001). Conclusion: Subjects with AD in whom eczema herpeticum develops have more severe TH2-polarized disease with greater allergen sensitization and more commonly have a history of food allergy, asthma, or both. They are also much more likely to experience cutaneous infections with S aureus or molluscum contagiosum. [Copyright &y& Elsevier]

Risk assessment of individuals with anaphylaxis is currently hampered by lack of (1) an optimal and readily available laboratory test to confirm the clinical diagnosis of an anaphylaxis episode and (2) an optimal method of distinguishing allergen-sensitized individuals who are clinically tolerant from those at risk for anaphylaxis episodes after exposure to the relevant allergen. Our objectives were to review the effector mechanisms involved in the pathophysiology of anaphylaxis; to explore the possibility of developing an optimal laboratory test to confirm the diagnosis of an anaphylaxis episode, and the possibility of improving methods to distinguish allergen sensitization from clinical reactivity; and to develop a research agenda for risk assessment in anaphylaxis. Researchers from the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergology and Clinical Immunology held a PRACTALL (Practical Allergy) meeting to discuss these objectives. New approaches being investigated to support the clinical diagnosis of anaphylaxis include serial measurements of total tryptase in serum during an anaphylaxis episode, and measurement of baseline total tryptase levels after the episode. Greater availability of the test for mature β-tryptase, a more specific mast cell activation marker for anaphylaxis than total tryptase, is needed. Measurement of chymase, mast cell carboxypeptidase A3, platelet-activating factor, and other mast cell products may prove to be useful. Consideration should be given to measuring a panel of mediators from mast cells and basophils. New approaches being investigated to help distinguish sensitized individuals at minimum or no risk from those at increased risk of developing anaphylaxis include measurement of the ratio of allergen-specific IgE to total IgE, determination of IgE directed at specific allergenic epitopes, measurement of basophil activation markers by using flow cytometry, and assessment of allergen-specific cytokine responses. Algorithms have been developed for risk assessment of individuals with anaphylaxis, along with a research agenda for studies that could lead to an improved ability to confirm the clinical diagnosis of anaphylaxis and to identify allergen-sensitized individuals who are at increased risk of anaphylaxis. [Copyright &y& Elsevier]

The article focuses on filaggrin gene (FLG), one of the most common and profound single-gene defects identified in the causation and modification of disease. Overview of how FLG was identified is presented, along with its genomics and cellular features. Clinical information on the diseases associated with FLG is given, including ichthyosis vulgaris, atopic dermatitis, allergic rhinitis and food allergy. Therapeutic approaches for FLG-associated diseases are also discussed.