Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. Methods:The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 + basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed | 1801 DUAN et Al.

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Background Multiplex tests allow for measurement of allergen‐specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta‐analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen‐specific IgE to peanut/tree nut allergens from three IgE test platforms. Methods Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high‐risk, pre‐school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL‐chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra‐test correlations between PR‐10 and nsLTP allergens were assessed. Results Using two regression methods, we demonstrated the ability to model allergen‐specific relationships with acceptable measures of fit (r2 = 94%‐56%) for peanut and tree nut sIgE testing at the extract and molecular‐level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. Conclusion Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta‐analysis.

Background: The nuclear factor κ-light-chain enhancer of activated B cells (NF-κB) signaling pathway is a critical regulator of many important adaptive and innate immune responses. The NF-κB transcription factor family consists of 5 structurally related core proteins, one of which is NFKB1. Mutations in the NFKB1 gene has been reported in patients with common variable immune deficiency (CVID) as well as with a large spectrum of clinical features including recurrent viral, bacterial, and fungal infections, autoimmunity, inflammation, and malignancy. Aim: We describe the clinical characteristics of a pediatric patient with a novel mutation in NFKB1. Methods: Patient informed consent was obtained in accordance with approved protocols from the Research Ethics Board at the Hospital for Sick Children. Gene panel testing was employed to identify the immune aberration. Results: Our patient, a previously well 18-month-old boy of Philippines descent, presented with multi-lineage cytopenias (thrombocytopenia, hemolytic anemia, neutropenia), splenomegaly, and lymphadenopathy. He did not have prior history of recurrent infections. Immunological work-up showed normal numbers of T and B cells, normal quantitative immunoglobulins, and adequate vaccination titres. Gene panel testing revealed a novel heterozygous missense variant c.425T>C (p. Ile142Thr) in the NFKB1 gene. Due to persistent cytopenias unresponsive to steroids and IVIG, he was started on Sirolimus with improvement in symptoms. Conclusion: NFKB1 encodes for p105, which is processed to generate the active p50 transcription factor that can interact with different proteins to activate or inhibit downstream signaling. Our patient was found to have a missense mutation in the Rel homology domain (RHD) of p50, which has distinct functions including DNA binding, protein dimerization, and inhibitory protein binding. The clinical presentation described here broadens the scope of characteristics associated with heterozygous NFKB1 mutations. Statement of novelty: We report a novel heterozygous missense variant c.425T>C (p. Ile142Thr) in the NFKB1 gene in a pediatric patient with cytopenias, lymphadenopathy, and splenomegaly. To the best of our knowledge, this variant has not been previously reported.

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