{"doi":"10.1111/cea.14587","title":"Whole Blood Transcriptomics Identifies Differences in Innate Immune Pathway Expression in Infants at Risk for Peanut Allergy","abstract":"Peanut allergy affects up to 2%–4% of children in the United States [1]. Despite advances in peanut allergy prevention through early introduction [2], there is limited understanding of molecular processes that drive development of peanut allergy. Similarly, differences between infants who tolerate peanut but demonstrate allergic sensitization and those with clinical reactivity to peanut are poorly understood. In a pilot study by our group, infants at high risk for peanut allergy demonstrated differential gene expression by clinical phenotype, but the magnitude of differences was not clinically significant given the variance of expression [3]. Further exploration of gene networks from differentially expressed gene (DEG) signatures may provide better targets for future studies. The primary objective of this study was to analyse the transcriptomic signature of a cohort of infants at risk for peanut allergy utilising whole blood RNA sequencing. We hypothesized that infants with peanut allergy would have differential expression of genes involved in immune pathways when compared to infants tolerant of peanut, with or without sensitization to peanut. Infants aged 4–11 months (n = 70) with peanut allergy risk factors (egg allergy, moderate to severe atopic dermatitis, or both) were recruited from Ann and Robert H. Lurie Children's Hospital of Chicago between 2018 and 2021. Subjects were classified as either peanut non-allergic (PNA), peanut sensitised (PS), or peanut allergic (PA). PA subjects had a convincing clinical history of reaction to peanut and peanut skin prick (SPT) wheal ≥ 3 mm or peanut SPT wheal ≥ 8 mm without history of consumption. Subjects regularly consuming peanut without history of an adverse reaction to peanut or who had never consumed peanut and had peanut SPT wheal size of 0–2 mm were classified as PNA. Infants who had ingested peanut without clinical reaction or passed a peanut oral food challenge (OFC) and had a peanut SPT wheal size of 3–7 mm or positive peanut specific IgE (sIgE) were classified as PS. RNA-seq was performed on whole blood. Deconvolution of gene expression by immune cell type showed no clinically significant differences between peanut allergy groups. Comparison of gene expression profiles by peanut allergy status was carried out using DESeq2 [4]. DEGs were split into upregulated and downregulated groups and were analysed separately in pathway analyses performed using Metascape [5]. Significant differences in single gene expression between groups were reported if there was ≥ ± absolute log2 fold change of 0.3 and FDR-corrected p ≤ 0.05. Half of the population was PNA (n = 35, 50%), 12 subjects (17%) were PS, and 23 subjects were PA (33%). Most subjects in each sub-group were male and had eczema. When adjusted for multiple comparisons, there were no statistically significant DEGs between PA and PNA subjects and PA and PS subjects. CLEC12B, a C-type lectin receptor exclusively expressed on skin mast cells, was up-regulated in PS versus PNA subjects (fold change 1.3, FDR p-value 0.012). Pathway analyses demonstrated upregulation of innate immune response, neutrophil degranulation, and cytokine signalling in PS as compared to PNA subjects. Inflammatory responses, innate immune responses, neutrophil degranulation, and regulation of immune effector processes were all down-regulated pathways in PA versus PS subjects (Figure 1). While there were few singly DEGs between peanut allergy groups, pathway analyses revealed several uniquely downregulated pathways in subjects with peanut allergy. The most highly down-regulated pathways in infants with peanut allergy as compared to those sensitised but tolerant to peanut were inflammatory and innate immune responses. The role of the innate immune response in molecular recognition of food allergens and the development of food allergy has been previously described [6, 7]. Our results of decreased innate immune signatures in PA subjects are in line with findings f","journal":"Clinical & Experimental Allergy","year":2024,"id":504829,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":586682,"name":"Samantha Gadd","orcid":"0000-0001-5033-8585","position":1,"is_corresponding":false},{"id":1139934,"name":"Lauren Gunderman","orcid":"0000-0003-3170-381X","position":2,"is_corresponding":false},{"id":1132534,"name":"Elizabeth Lippner","orcid":"0000-0002-5148-3394","position":3,"is_corresponding":false},{"id":932788,"name":"Ashley L. Devonshire","orcid":"0000-0002-6341-5794","position":4,"is_corresponding":false},{"id":722832,"name":"Matthew J. Schipma","orcid":"0000-0002-0865-1057","position":5,"is_corresponding":false},{"id":245518,"name":"Sergejs Berdnikovs","orcid":"0000-0001-5186-3293","position":6,"is_corresponding":false},{"id":247344,"name":"Rajesh Kumar","orcid":"0000-0002-1962-7108","position":7,"is_corresponding":false},{"id":971343,"name":"Abigail Lang","orcid":"0000-0002-0186-691X","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T02:10:43.302033Z","pmid":"39415357","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}