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Systemic sclerosis patients showed elevated CXCL4 protein
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Patients with systemic sclerosis experienced greater levels of the CXCL4 protein compared with patients with systemic lupus erythematosus, ankylosing spondylitis, liver fibrosis and healthy controls, according to study results.
Researchers studied 462 patients with limited cutaneous systemic sclerosis (SSc; mean age at onset, 42.4 years; 82% women) and 317 patients with diffuse cutaneous SSc (mean age at onset, 43.8 years; 69% women). Plasmacytoid dendritic cells from patients with SSc and healthy controls were isolated. Proteome-wide analysis was conducted, with results validated in five cohorts of patients with SSc. The results were compared with 109 patients with systemic lupus erythematosus (SLE), 93 patients with ankylosing spondylitis (AS) and 93 patients with liver fibrosis. Plasma levels of CXCL4 protein were correlated with SSc features, and direct effects of CXCL4 in vitro and in vivo were observed.
“Proteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in [SSc], both in circulation and in skin,” the researchers wrote.
Patients with SSc had a significantly greater mean level of CXCL4 (25,624 ± 2,652 pg/mL) compared with controls (92.5 ± 77.9 pg/mL), and patients with SLE (1,346 ± 1,011 pg/mL), AS (1,368 ± 1,162 pg/mL) or liver fibrosis (1,668 ± 1,263 pg/mL). Skin and lung fibrosis and pulmonary arterial hypertension displayed a correlation with CXCL4 levels.
CXCL4 was the only chemokine predicting systemic sclerosis risk and progression.
“In vivo, CXCL4 downregulated expression of transcription factor FLI1, induced markers of endothelial-cell activation, and potentiated responses of toll-like receptors,” the researchers reported. “In vivo, CXL4 induced the influx of inflammatory cells and skin transcription changes, as in [SSc].”
“Our observations suggest that CXCL4 and plasmacytoid dendritic cells are central to the pathogenesis of [SSc],” the researchers concluded. “The levels of CXCL4 correlated well with the level of fibrosis and the occurrence and progression of pulmonary arterial hypertension, the two clinical hallmarks of this disorder.”
Disclosure: See the study for a full list of relevant financial disclosures.
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