Primary Data Supporting "Asthmatics with High Serum Amyloid A have Pro-inflammatory HDL: Implications for Augmented Systemic and Airway Inflammation", Figures 2 - 8, E1 - E9, DOI: https://doi.org/10.1016/j.jaci.2023.11.917

Rationale: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of asthmatics, it is not known whether this modifies asthma severity.

Objective: To define the clinical characteristics of asthmatics with high SAA levels and assess whether HDL from SAA-high asthmatics is pro-inflammatory.

Methods: SAA levels in serum from asthmatic and non-asthmatic subjects were quantified by ELISA. HDL isolated from asthmatics with high SAA levels were used to stimulate human monocytes and were intravenously administered to BALB/c mice.

Results: A SAA level > 108.8 mg/ml was defined as the threshold to identify 11% of an asthmatic cohort (n = 146) as being SAA-high. SAA-high asthmatics were characterized by increased serum C-reactive protein, IL-6, and TNF-a; older age; and an increased prevalence of obesity and severe asthma. HDL isolated from SAA-high asthmatics (SAA-high HDL) had an increased content of SAA as compared to HDL from SAA-low asthmatics and induced the secretion of IL-6, IL-1b and TNF-a from human monocytes via a FPR2/ATP/P2X7R axis. Intravenous administration to mice of SAA-high HDL, but not normal HDL, induced systemic inflammation and amplified allergen-induced neutrophilic airway inflammation and goblet cell metaplasia.

Conclusion: SAA-high asthmatics are characterized by systemic inflammation, older age, and an increased prevalence of obesity and severe asthma. HDL from SAA-high asthmatics is pro-inflammatory and, when intravenously administered to mice, induces systemic inflammation, and amplifies allergen-induced neutrophilic airway inflammation. This suggests that systemic inflammation induced by SAA-high HDL may augment disease severity in asthma.