RESUMO
Mechanisms driving acute food allergic reactions have not been fully characterized. We profile the dynamic transcriptome of acute peanut allergic reactions using serial peripheral blood samples obtained from 19 children before, during, and after randomized, double-blind, placebo-controlled oral challenges to peanut. We identify genes with changes in expression triggered by peanut, but not placebo, during acute peanut allergic reactions. Network analysis reveals that these genes comprise coexpression networks for acute-phase response and pro-inflammatory processes. Key driver analysis identifies six genes (LTB4R, PADI4, IL1R2, PPP1R3D, KLHL2, and ECHDC3) predicted to causally modulate the state of coregulated networks in response to peanut. Leukocyte deconvolution analysis identifies changes in neutrophil, naive CD4+ T cell, and macrophage populations during peanut challenge. Analyses in 21 additional peanut allergic subjects replicate major findings. These results highlight key genes, biological processes, and cell types that can be targeted for mechanistic study and therapeutic targeting of peanut allergy.
Assuntos
Reação de Fase Aguda/genética , Hipersensibilidade a Amendoim/genética , RNA Mensageiro/metabolismo , Reação de Fase Aguda/imunologia , Adolescente , Linfócitos T CD4-Positivos/imunologia , Criança , Método Duplo-Cego , Enoil-CoA Hidratase/genética , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Inflamação/genética , Inflamação/imunologia , Macrófagos/imunologia , Masculino , Proteínas dos Microfilamentos/genética , Proteínas do Tecido Nervoso/genética , Neutrófilos/imunologia , Hipersensibilidade a Amendoim/imunologia , Proteína Fosfatase 1/genética , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas/genética , Distribuição Aleatória , Receptores Tipo II de Interleucina-1/genética , Receptores do Leucotrieno B4/genética , Reprodutibilidade dos TestesRESUMO
Meditation is becoming increasingly practiced, especially for stress-related medical conditions. Meditation may improve cellular health; however, studies have not separated out effects of meditation from vacation-like effects in a residential randomized controlled trial. We recruited healthy women non-meditators to live at a resort for 6 days and randomized to either meditation retreat or relaxing on-site, with both groups compared with 'regular meditators' already enrolled in the retreat. Blood drawn at baseline and post intervention was assessed for transcriptome-wide expression patterns and aging-related biomarkers. Highly significant gene expression changes were detected across all groups (the 'vacation effect') that could accurately predict (96% accuracy) between baseline and post-intervention states and were characterized by improved regulation of stress response, immune function and amyloid beta (Aß) metabolism. Although a smaller set of genes was affected, regular meditators showed post-intervention differences in a gene network characterized by lower regulation of protein synthesis and viral genome activity. Changes in well-being were assessed post intervention relative to baseline, as well as 1 and 10 months later. All groups showed equivalently large immediate post-intervention improvements in well-being, but novice meditators showed greater maintenance of lower distress over time compared with those in the vacation arm. Regular meditators showed a trend toward increased telomerase activity compared with randomized women, who showed increased plasma Aß42/Aß40 ratios and tumor necrosis factor alpha (TNF-α) levels. This highly controlled residential study showed large salutary changes in gene expression networks due to the vacation effect, common to all groups. For those already trained in the practice of meditation, a retreat appears to provide additional benefits to cellular health beyond the vacation effect.
