Serum pulmonary and activation‐regulated chemokine/CCL18 levels in patients with systemic sclerosis: A sensitive indicator of active pulmonary fibrosis

Abstract

Objective. To clarify the clinical significance of serum levels of pulmonary and activation-regulated chemokine (PARC) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc) and to compare PARC levels with KL-6 antigen or surfactant protein D (SP-D) levels.Methods. Serum PARC levels were determined by enzyme-linked immunosorbent assay in 123 SSc patients. In a retrospective longitudinal study, correlation of serum PARC levels with the activity of PF was assessed in 21 SSc patients with active PF.Results. PARC levels at the first visit were higher in patients with SSc than in patients with systemic lupus erythematosus (SLE) or healthy controls. Increased serum PARC levels were associated with involvement of PF, decreased diffusing capacity for carbon monoxide, and decreased vital capacity in SSc patients. In the longitudinal study, serum PARC levels were significantly decreased in SSc patients with inactive PF compared with those with active PF.Conclusion. Elevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL-6 or SP-D levels in SSc.Serum PARC levels may be a useful new serum marker for active PF in SSc.

Systemic sclerosis: a prototypic multisystem fibrotic disorder

“…In vitro, MCP-1 stimulates collagen production directly or indirectly through the induction of endogenous TGF-β and IL-4 (89). Levels of MCP-1 and of multiple other chemokines are elevated in the serum and bronchoalveolar lavage fluid from patients with SSc and correlate with the severity of fibrosis (90,91). The expression of MCP-1 and MCP-3 and of their receptors is markedly elevated in lesional skin and cultured fibroblasts from patients with SSc, particularly in early-stage disease (92,93).…”

Molecular biomarkers in idiopathic pulmonary fibrosis

“…CCL18. CC chemokine ligand 18 (CCL18), also known as PARC (for pulmonary and activation-regulated chemokine), is a chemokine protein produced by alveolar macrophages that stimulates collagen production in pulmonary fibroblasts (40,71,72). In fibrotic ILDs including IPF, there are increased numbers of CCL18-positive macrophages (71).…”

Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis

“…CC chemokine ligand (CCL)18 is a chemokine secreted mainly by alveolar macrophages (M2 phenotype) [2] alternatively activated by T-helper cell type 2 cytokines and plays an important role in the immune-mediated lung fibrosis processes in idiopathic pulmonary fibrosis (IPF) [3] and scleroderma lung disease [3,4]. A high amount of CCL18 produced by alveolar inflammatory cells [5] could induce an overproduction of collagen by lung fibroblasts through Sp1 signalling and basal Smad3 activity, independently of autocrine transforming growth factor-b [6,7].…”

“…Serum CCL18 fulfilled criteria for a potential biomarker of lung fibrosis activity in ILD associated with SSc [3,4]. Its prognostic value on lung function worsening over time in patients with SSc has not yet been prospectively assessed in a longterm follow-up study.…”