Allergy & Immunology

EGPA airways show IFN-driven granulocytes and IGF1+ macrophages as therapeutic candidates

Single-cell RNA-seq showed EGPA airway inflammation is dominated by type I IFN pathways, whereas severe eosinophilic asthma (SEA) is TNF-predominant. IL1B+MX1+ neutrophils in EGPA expressed IFN-stimulated genes and promoted tertiary lymphoid structure formation with autoantibody production. Additional IFN-activated granulocytes, including APOC1+ eosinophils, SCN7A+ mast cells, and basophils, contributed to EGPA-specific immune dysregulation. Longitudinal profiling identified IGF1+ macrophages linked to EGPA relapse, suggesting a relapse-associated and potentially targetable myeloid population. IGF1 blockade in animal models of EGPA and SEA reduced type 2 inflammation, mucin production, and goblet cell hyperplasia, nominating IGF1 as a druggable node. 1

Type 2 IgG memory B cells and long-lived IgE plasma cells sustain allergy

This review explains how allergic IgE responses persist despite scarce IgE memory B cells and short serum IgE half-life. High-affinity IgE is generated via sequential class switching from affinity-matured non-IgE, type 2 IgG memory B cells. These allergen-specific IgG memory cells are poised to reclass-switch to IgE, rapidly regenerating IgE after re-exposure or treatment withdrawal. Long-lived IgE plasma cells in bone marrow and secondary lymphoid organs provide stable allergen-specific IgE production over time. Targeting these memory IgG2 and long-lived IgE plasma compartments is highlighted as essential for durable disease modification in allergy. 2

Systematic review exposes weak comparative data for FESS versus biologics in CRSwNP

This systematic review and meta-analysis compared sinonasal outcomes after functional endoscopic sinus surgery (FESS) versus biologic therapy for CRSwNP. Biologics mainly targeted type 2 inflammation, including dupilumab, omalizumab, and mepolizumab, often in patients with asthma or AERD. Direct head-to-head comparisons between FESS and biologics were scarce, limiting conclusions about relative efficacy and durability. Heterogeneous real-world study designs and patient populations further constrained quantitative comparisons. Clinicians must currently individualize FESS versus biologic sequencing using comorbidities, access, and patient preference rather than robust comparative evidence. 3

Biologics benefit severe asthma patients even when baseline FEV1 is normal

This CHRONICLE analysis assessed biologic effectiveness in severe asthma with normal (FEV1 ≥80% predicted) versus reduced pre-bronchodilator FEV1. Among 233 adults, 28.8% had normal lung function despite severe asthma and frequent exacerbations. Biologic initiation reduced annualized exacerbation rates by 50% in the normal-lung-function group and by 59% in those with reduced FEV1. Exacerbation-related emergency department visit rates fell by 44% and 63% in the normal and reduced lung function groups, respectively. These data support biologic eligibility discussions based on exacerbation burden and severity rather than relying solely on spirometric impairment. 4