Abstract
Inflammation in systemic sclerosis (SSc) is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA), a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.
Highlights
Systemic sclerosis (SSc) is a chronic multisystem disease associated with immune dysregulation, vascular injury and fibrosis [1]
Stage dcSSc was associated with higher serum amyloid A (SAA) levels compared with late-stage disease (U = 222, p = 0.08), whereas an opposite trend was seen in patients with lcSSc (U = 269, p = 0.02) (Fig. 1B)
We show here that circulating levels of the inflammatory marker SAA are elevated in patients with SSc
Summary
Systemic sclerosis (SSc) is a chronic multisystem disease associated with immune dysregulation, vascular injury and fibrosis [1]. Progressive fibrosis in the skin and lungs are prominent, and leads to organ failure accounting for the substantial mortality of SSc [2]. Inflammatory infiltrates are observed in a variety of affected organs in early-stage disease [3,4,5] and are accompanied by elevated circulating levels of inflammatory cytokines and chemokines. SAA Is a Marker of Pulmonary Involvement in SSc
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