A B S T R A C TBackground: The increasing incidence of pediatric food allergy results in significant health care burden and family stress. Oral immunotherapy (OIT) can induce tolerance to peanut, milk, and egg. OIT for other foods, particularly multiple foods simultaneously, has not been thoroughly studied. Objective: To summarize our experience with OIT for multiple foods in a pediatric allergy clinic setting. Methods: Medical records were reviewed for patients undergoing OIT for multiple foods. Methods and outcomes of OIT were summarized. Outcomes were analyzed for correlation with baseline food allergen skin prick tests (SPTs) and specific IgE (sIgE) test results. Results: Forty-five patients aged 1.5 to 18 years undertook OIT for up to 12 foods, including peanut, tree nuts, seeds, legumes, and egg. At the time of review, 35 patients were receiving daily maintenance dosing, 4 had completed OIT and were continuing to eat their foods 3 times weekly, and 6 had stopped OIT because of anxiety, inconvenience, or allergy symptoms. A total of 49% of patients had reactions during the up-dosing process, mostly oral itching (33%), perioral hives (40%), and abdominal pain (35%). There was no correlation of baseline skin prick test (SPT) and sIgE test results with reaction threshold for baseline food challenge, lowest dose causing reactions during up-dosing, or time to reach maintenance. Higher baseline sIgE level but not baseline SPT result was associated with an increased number of allergic reactions during OIT. Baseline SPT correlated with stopping OIT. Conclusion: A similar approach to that used for peanut OIT can be taken for nonpeanut foods and for multiple foods simultaneously. High baseline allergy test results are not a contraindication to OIT.
CpG) award. M.T.W. is supported by the NIH (grant no. R01 NS099068), a Cincinnati Children's Research Foundation Endowed Scholar Award, and a CCHMC CpG award. M.E.R.'s work is funded by the NIH (grant nos. R37 AI045898, U19 AI070235, R01 AI057803, R01 HG010730, and R01 AR073228); the Campaign Urging Research for Eosinophilic Disease; and the Sunshine Charitable Foundation and its supporters, Denise and David Bunning. This study was originally funded by the Consortium of Food Allergy Researchers (COFAR, National Institute of Allergy and Infectious Diseases grant no. U19AI066738). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Disclosure of potential conflict of interest: V. Mukkada is a consultant for Shire, a Takeda company. T. Wen is a coinventor of the EoE diagnostic panel, a patent owned by Cincinnati Children's Hospital Medical Center, and serves as a consultant for NanoString Technologies, Inc, and a consultant committee member for GlaxoSmithKline. M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celgene, Astra Zeneca, Arena Pharmaceuticals, Guidepoint, and Suvretta Capital Management; has an equity interest in the first 5 listed and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate; and is an inventor of patents owned by Cincinnati Children's Hospital Medical Center. The rest of the authors declare that they have no relevant conflicts of interest.
Atopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated the potential epigenetic mechanisms responsible for the genetic susceptibility of CD4+ T cells. To understand the differences in gene regulatory activity in peripheral blood T cells in AD, we measured chromatin accessibility (an assay based on transposase-accessible chromatin sequencing, ATAC-seq), nuclear factor kappa B subunit 1 (NFKB1) binding (chromatin immunoprecipitation with sequencing, ChIP-seq), and gene expression levels (RNA-seq) in stimulated CD4+ T cells from subjects with active moderate-to-severe AD, as well as in age-matched and non-allergic controls. Open chromatin regions in stimulated CD4+ T cells were highly enriched for AD genetic risk variants, with almost half of the AD risk loci overlapping AD-dependent ATAC-seq peaks. AD-specific open chromatin regions were strongly enriched for NF-κB DNA-binding motifs. ChIP-seq identified hundreds of NFKB1-occupied genomic loci that were AD- or control-specific. As expected, the AD-specific ChIP-seq peaks were strongly enriched for NF-κB DNA-binding motifs. Surprisingly, control-specific NFKB1 ChIP-seq peaks were not enriched for NFKB1 motifs, but instead contained motifs for other classes of human transcription factors, suggesting a mechanism involving altered indirect NFKB1 binding. Using DNA sequencing data, we identified 63 instances of altered genotype-dependent chromatin accessibility at 36 AD risk variant loci (30% of AD risk loci) that might lead to genotype-dependent gene expression. Based on these findings, we propose that CD4+ T cells respond to stimulation in an AD-specific manner, resulting in disease- and genotype-dependent chromatin accessibility alterations involving NFKB1 binding.
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