Allergy & Immunology

Benralizumab significantly reduces flares in PDGFRA‑negative hypereosinophilic syndrome

In the phase 3 NATRON trial, 133 FIP1L1::PDGFRA‑negative HES patients received benralizumab 30 mg every 4 weeks or placebo plus background therapy. Benralizumab reduced risk of first HES flare versus placebo (hazard ratio 0.35, 95% CI 0.18–0.69; P = 0.0024). Overall adverse event rates were similar with benralizumab and placebo, and safety matched the established profile from asthma indications. These data support benralizumab as an effective add‑on option for PDGFRA‑negative HES in patients with recurrent disease despite standard therapy. 1

Primary immunodeficiency genes are enriched and over‑expressed in systemic lupus erythematosus

This study assembled a database of 453 primary immunodeficiency (PID) genes and evaluated their relationship to systemic lupus erythematosus (SLE). PID genes overlapped SLE risk loci more than expected by chance and more than with risk alleles of other autoimmune diseases. PID genes were frequently differentially expressed and generally over‑expressed in SLE blood and immune cell subsets, especially in active disease. Gene expression patterns in PID clusters classified SLE versus controls and active versus inactive SLE with accuracies of 0.80 and 0.74, respectively. Findings link pathways governing host defense to SLE pathogenesis and highlight PID genes as potential therapeutic or biomarker targets. 2

Tim‑3 agonism suppresses ILC2s and attenuates airway hyperreactivity in experimental asthma

This mechanistic study identifies Tim‑3 as an inhibitory checkpoint on pulmonary group 2 innate lymphoid cells (ILC2s) in allergic asthma models. Tim‑3 expression increased on activated lung ILC2s, and Tim‑3 agonists reduced ILC2 proliferation and type 2 cytokine production via the NLK pathway. Tim‑3 engagement also suppressed mitochondrial metabolism in ILC2s, further limiting their effector function. In IL‑33‑ and Alternaria‑induced airway hyperreactivity models, Tim‑3 agonists reduced airway hyperreactivity, whereas ILC2‑specific Tim‑3 deletion worsened disease. Similar inhibitory effects were observed in human ILC2s and humanized mice, suggesting Tim‑3 agonism as a potential therapeutic strategy for allergic asthma. 3