Asthmatic patients with high serum amyloid A have proinflammatory HDL: Implications for augmented systemic and airway inflammation

Abstract

RationaleSerum 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. ObjectiveTo define the clinical characteristics of asthmatics with high SAA levels and assess whether HDL from SAA-high asthmatics is pro-inflammatory. MethodsSAA 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. ResultsA SAA level > 108.8 μg/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-α; 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-1β and TNF-α 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. ConclusionSAA-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.