Advances in Immunotherapy for Food Allergy

Food allergy is a life-threatening allergic disease that is increasing in prevalence with no approved curative therapy. Standard treatment of food allergy is limited to avoidance of the allergen and supportive management of allergic symptoms and anaphylaxis. Current research, however, has been focused on developing therapy that can modify the allergic immune response in both allergen-specific and non-specific methods. This review will provide an overview of these methods including oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, modified food protein vaccines, anti-IgE monoclonal antibody adjuvant therapy, Chinese herbs, and helminth therapy

Factors influencing age of common allergen introduction in early childhood

ObjectivesWe evaluated factors influencing the timing of allergen introduction in the U.S., including updated peanut introduction guidelines.Study designThe Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) study is a prospective observational cohort in suburban Massachusetts. Infants' caregivers enrolled between 2014 and 2017, and they reported when they introduced common allergens to their child. Multivariable linear and survival regression analyses were used to examine factors influencing time of introduction of allergens.ResultsBy 9 months, children old enough to be potentially affected by NIAID's 2017 peanut introduction guidelines were more often introduced to peanut than children enrolled well before guidelines publication [54% vs. 42%, OR: 1.63, CI: (1.03, 2.57), P = 0.03]. At any given time, Black children were 73% [HR: 0.27, CI: (0.11, 0.69), P = 0.006] less likely to be introduced to peanut as early as White children. Asian children were, respectively, 36% [HR: 0.64, CI: (0.47, 0.86), P = 0.003] and 26% [HR: 0.74, CI: (0.55, 0.97), P = 0.03] less likely to be introduced to peanut and egg as early as White children. A first child was 27% [HR: 1.27, CI: (1.04, 1.56), P = 0.02] more likely to have been introduced to peanut earlier than a non-first child. There was no association between age of introduction and sex, gestational age, family history of food allergy, or other allergic comorbidities.ConclusionUpdated introduction guidelines, race, and birth order all influenced earlier introduction of peanut. Further studies to evaluate current practices for allergen introduction with a focus on potential disparities are needed

Novel baseline predictors of adverse events during oral immunotherapy in children with peanut allergy

Though peanut oral immunotherapy (OIT) is a promising investigational therapy, its potential is limited by substantial adverse events (AEs), which are relatively understudied

Infant head growth in male siblings of children with and without autism spectrum disorders

Previous research has indicated that children with autism exhibit accelerated head growth (HG) in infancy, although the timing of acceleration varies between studies. We examined infant HG trajectory as a candidate autism endophenotype by studying sibling pairs. We retrospectively obtained serial head orbitofrontal circumference measurements of: a) 48 sibling pairs in which one (n = 28) or both (n = 20) sibs were affected by an autism spectrum disorder (ASD); and b) 85 control male sibling pairs. Rate of HG of ASD subjects was slightly accelerated compared to controls, but the magnitude of difference was below the limit of reliability of standard measurement methods. Sibling intra class correlation for rate of HG was highly statistically significant; the magnitude was significantly stronger among autism-affected families (ICC = .63) than among controls (ICC = .26), p < .01. Infant HG trajectory appears familial—possibly endophenotypic—but was not a reliable marker of autism risk among siblings of ASD probands in this sample

Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy

Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy

Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals

Recent advances in high-throughput T cell receptor (TCR) sequencing have allowed for new insights into the human TCR repertoire. However, methods for capturing antigen-specific repertoires remain an area of development. Here, we describe a potentially novel approach that utilizes both a biological and statistical enrichment to define putatively antigen-specific complementarity-determining region 3 (CDR3) repertoires in unselected individuals. The biological enrichment entailed FACS of in vitro antigen-activated memory CD4+ T cells, followed by TCRβ sequencing. The resulting TCRβ sequences were then filtered by selecting those that are statistically enriched when compared with their frequency in the autologous resting T cell compartment. Applying this method to define putatively peanut protein-specific repertoires in 27 peanut-allergic individuals resulted in a library of 7345 unique CDR3β amino acid sequences that had similar characteristics to other validated antigen-specific repertoires in terms of homology and diversity. In-depth analysis of these CDR3βs revealed 36 public sequences that demonstrated high levels of convergent recombination. In a network analysis, the public CDR3βs were shown to be core sequences with more edges than their private counterparts. This method has the potential to be applied to a wide range of T cell-mediated disorders and to yield new biomarkers and biological insights

Expansion of the CD4+ effector T-cell repertoire characterizes peanut-allergic patients with heightened clinical sensitivity

© 2019 American Academy of Allergy, Asthma & Immunology Background: Individuals with peanut allergy range in clinical sensitivity: some can consume grams of peanut before experiencing any symptoms, whereas others suffer systemic reactions to 10 mg or less. Current diagnostic testing only partially predicts this clinical heterogeneity. Objective: We sought to identify characteristics of the peanut-specific CD4+ T-cell response in peanut-allergic patients that correlate with high clinical sensitivity. Methods: We studied the T-cell receptor β-chain (TCRβ) usage and phenotypes of peanut-activated, CD154+ CD4+ memory T cells using fluorescence-activated cell sorting, TCRβ sequencing, and RNA-Seq, in reactive and hyporeactive patients who were stratified by clinical sensitivity. Results: TCRβ analysis of the CD154+ and CD154− fractions revealed more than 6000 complementarity determining region 3 sequences and motifs that were significantly enriched in the activated cells and 17% of the sequences were shared between peanut-allergic individuals, suggesting strong convergent selection of peanut-specific clones. These clones were more numerous among the reactive patients, and this expansion was identified within effector, but not regulatory T-cell populations. The transcriptional profile of CD154+ T cells in the reactive group skewed toward a polarized TH2 effector phenotype, and expression of TH2 cytokines strongly correlated with peanut-specific IgE levels. There were, however, also non–TH2-related differences in phenotype. Furthermore, the ratio of peanut-specific clones in the effector versus regulatory T-cell compartment, which distinguished the clinical groups, was independent of specific IgE concentration. Conclusions: Expansion of the peanut-specific effector T-cell repertoire is correlated with clinical sensitivity, and this observation may be useful to inform our assessment of disease phenotype and to monitor disease longitudinally

Partial Least Squares Discriminant Analysis and Bayesian Networks for Metabolomic Prediction of Childhood Asthma

To explore novel methods for the analysis of metabolomics data, we compared the ability of Partial Least Squares Discriminant Analysis (PLS-DA) and Bayesian networks (BN) to build predictive plasma metabolite models of age three asthma status in 411 three year olds (n = 59 cases and 352 controls) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) study. The standard PLS-DA approach had impressive accuracy for the prediction of age three asthma with an Area Under the Curve Convex Hull (AUCCH) of 81%. However, a permutation test indicated the possibility of overfitting. In contrast, a predictive Bayesian network including 42 metabolites had a significantly higher AUCCH of 92.1% (p for difference &lt; 0.001), with no evidence that this accuracy was due to overfitting. Both models provided biologically informative insights into asthma; in particular, a role for dysregulated arginine metabolism and several exogenous metabolites that deserve further investigation as potential causative agents. As the BN model outperformed the PLS-DA model in both accuracy and decreased risk of overfitting, it may therefore represent a viable alternative to typical analytical approaches for the investigation of metabolomics data

Additional file 3 of Longitudinal disease-associated gut microbiome differences in infants with food protein-induced allergic proctocolitis

Additional file 3: Supplemental Table 2. Summary table of all significant MaAsLin results. All MaAsLin results from 16S rRNA gene sequencing with q-values for significant taxa which met our predetermined threshold for significance (q<0.20). Mixed effects linear models using arcsine transform on relative abundances were used to determine significance. p-values were adjusted for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR) method with FDR set at <0.20. (XLS 224 kb