Showing papers by "Scott H. Sicherer published in 2016"

Early-life gut microbiome composition and milk allergy resolution

Abstract: 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.

Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy

Abstract: 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.

Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness.

Abstract: Background In a previously reported CoFAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy (eOIT). Active treatment induced desensitization in most and sustained unresponsiveness (SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. Methods Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white (EW)-, ovalbumin (OVA)-, and ovomucoid (OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using ImmunoCAP®. Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. Results No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE-OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE-EW (P = 0.038), IgE-OVM (P = 0.032), and a higher IgG4/IgE-OVM ratio (P = 0.013) were associated with clinical response. Relative increases in IgG4-EW, IgA-EW, and IgA2-EW were observed in responders (P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders (P = 0.004, 0.009, 0.028, and 0.008, respectively). Conclusions Increased IgG4-EW, IgA-EW, and IgA2-EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE-EW and IgE-OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers.

Diagnosis and management of food allergy

Abstract: Food allergy is estimated to affect 2%–10% of the population, with higher rates among children than among adults.[1][1] The prevalence of childhood food allergies has apparently increased, with the US Centers for Disease Control and Prevention reporting an increase from 3.4% to 5.1% between 1997

Interpreting IgE sensitization tests in food allergy

Abstract: Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.

Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype.

Abstract: Background Egg allergy is one of the most common food allergies of childhood There is a lack of information on the immunologic basis of egg allergy beyond the role of IgE Objective To use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy Methods Peripheral blood mononuclear cells (PBMCs) were obtained from egg-allergic children who were defined as reactive (BER) or tolerant (BET) to baked egg, and from food allergic controls (AC) who were egg non-allergic PBMCs were stimulated with egg white protein Gene transcription was measured by microarray after 24 h, and cytokine secretion by multiplex assay after 5 days Results The transcriptional response of PBMCs to egg protein differed between BER and BET versus AC subjects Compared to the AC group, the BER group displayed increased expression of genes associated with allergic inflammation as well as corresponding increased secretion of IL-5, IL-9 and TNF-α A similar pattern was observed for the BET group Further similarities in gene expression patterns between BER and BET groups, as well as some important differences, were revealed using a novel Immune Annotation resource developed for this project This approach identified several novel processes not previously associated with egg allergy, including positive associations with TLR4-stimulated myeloid cells and activated NK cells, and negative associations with an induced Treg signature Further pathway analysis of differentially expressed genes comparing BER to BET subjects showed significant enrichment of IFN-α and IFN-γ response genes, as well as genes associated with virally-infected DCs Conclusions Transcriptional profiling identified several novel pathways and processes that differed when comparing the response to egg allergen in BET, BER, and AC groups We conclude that this approach is a useful hypothesis-generating mechanism to identify novel immune processes associated with allergy and tolerance to forms of egg

Global perceptions of food allergy thresholds in 16 countries

Abstract: Childhood food allergy is a significant public health issue with prevalence rates as high as 10% among children in some countries (1, 2). While the quality and quantity of global data on childhood food allergy have increased in recent years, knowledge on consumer perceptions of issues affecting management is lacking (3, 4). Allergic reactions to food can vary from mild to life-threatening. As a result, the standard recommendation is to strictly avoid the food allergen, which can be complicated when purchasing packaged food. The food industry in most countries is required to label the presence of the most common food allergens when they are ingredients in packaged foods; however, they may voluntarily add precautionary allergen labeling (PAL). These statements, such as ‘may contain. . .’ or ‘processed in a facility that manufactures. . .’, are unregulated, and it is unknown how many products with PAL actually contain trace levels. Consumers must make their own decisions on how to interpret these PAL statements, which can lead to food restrictions that affect the daily lives and well-being of consumers and caregivers (5, 6). A greater understanding of food allergen thresholds (the lowest amount of a food allergen that can cause an allergic reaction) is important to a variety of food allergy stakeholders (7). In 2011, an expert panel was assembled to establish reference doses for 11 allergenic foods as part of the VITAL (Voluntary Incidental Trace Allergen Labeling) program. The doses were obtained from clinical challenges of individuals to establish an eliciting dose for each food at which only a predicted 1–3% of the population would react (8). This study represents the first of its kind to examine differences in perceptions about food allergen thresholds and PAL from the perspective of consumers in 16 countries across the world.

Doctor, my child is bullied: food allergy management in schools.

Abstract: PURPOSE OF REVIEW: Studies suggest that food allergies have increased in prevalence, resulting in most school classrooms having more than one child affected. Children with food allergies are vulnerable for experiencing potentially life-threatening allergic reactions, as well as social consequences such as bullying. Management recommendations for food allergies in schools should incorporate knowledge of both issues. RECENT FINDINGS: Current recommendations for food allergy management in schools focus on appropriate avoidance measures and prompt recognition and treatment of allergic reactions. Guidelines focus upon a school-wide approach, with comprehensive involvement of many stakeholders, but individual students require specific emergency action plans. Special risk groups include young children who need additional supervision and adolescents who may take risks. Based on the observation that anaphylaxis can occur in persons without a prior diagnosis, having epinephrine available for prompt first-aid management of any student in need is now recommended. To promote socialization, avoidance measures should minimize separation of children with food allergies from their peers. Parents and schools need to be aware of bullying and implement intervention and prevention measures. SUMMARY: Management recommendations for food allergies in schools should ensure the safety of the child, address bullying, and avoid unnecessary isolation. Language: en