Serum calprotectin elevation and interferon-α-induced neutrophil priming in macrophage activation syndrome associated with systemic lupus erythematosus: Clinical and experimental insights

OBJECTIVES: To clarify the diagnostic utility of serum calprotectin and gene expression in interferon (IFN)-α-activated neutrophils in macrophage activation syndrome (MAS) in patients with systemic lupus erythematosus (SLE). METHODS: This single-centre, cross-sectional study analysed serum calprotectin levels in 47 patients with SLE (including eight with MAS) and 7 patients with adult-onset Still's disease (AOSD) complicated with MAS as a reference population. In neutrophil-based experiments, mRNA expression levels of S100A8 and S100A9 were measured following stimulation with IFN-α or interleukin (IL)-1β. RESULTS: Serum calprotectin levels were significantly elevated in patients with SLE-MAS compared to those with SLE without MAS and comparable to those in patients with AOSD-MAS. Calprotectin levels correlated with serum ferritin levels (rs = 0.49, P = .004), but not with anti-dsDNA antibodies or complement levels. At a cut-off value of 9184.4 ng/ml, serum calprotectin demonstrated sensitivity of 62.5% and specificity of 94.9% for identifying MAS. Recombinant IFN-α2a induced a dose-dependent increase in S100A8 and S100A9 expression in neutrophils, whereas recombinant interleukin-1β had no effect. Pre-treatment with an anti-IFN-α2 neutralising antibody effectively suppressed the IFN-α2a-induced expression of S100A8 and S100A9. CONCLUSIONS: Serum calprotectin, upregulated by IFN-α, may serve as a useful biomarker for diagnosing MAS in SLE.