Charcot-Leyden crystals are associated with airway autoimmune responses in severe asthma

Résumé fourni par la source

Rationale: Airway autoantibodies induce histone-coated eosinophil extracellular traps (EETs). EETs are associated with free eosinophil granules (FEGs) and galectin-10 which autocrystallize ex vivo to form Charcot-Leyden crystals (CLCs). Objective: To investigate cytokines and autoimmune responses in patients with CLCs. Methods: Between 2020-2022, CLCs and cell differentials were routinely reported for processed sputum. Cell-free supernatants were assessed for antinuclear antibodies (HUMAN Diagnostics, PMID 28751233), cytokines (EllaTM, Protein Simple), and danger-associated molecular patterns (DAMPs): high mobility box group 1 (HMGB1) and galectin-10 proteins (Novus Biologicals). Results: CLCs were reported in 61/3075 (2%) processed sputa slides (protocol: PMID 8804934). All 46 CLC+ samples with adequate volume and confirmed severe asthma diagnosis were eosinophilic (≥3% eos±FEGs) and comprised the Eos+CLC+ group. Additionally, Eos+CLC- (n=53) and Eos-CLC- (n=32) were included for analysis. Eos+CLC+ had increased ANAs vs CLC- groups (P<0.005, Fig 1A). Reactivities against anti-histone IgG were higher in Eos+CLC+ (96%) vs. Eos-CLC- (30%) (Fig 1B). Eos+CLC+ had higher T2 inflammation (IL-4, IL-5, IL-13, P<0.05), HMGB1 (Fig 1C), and decreased trend for “free” galactin-10 compared to CLC- sputa. Conclusions: We report that severe asthma patients with CLCs have high autoimmune burden marked by DAMPs and autoantibodies.

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