Lakota Katja, Carns Mary, Podlusky Sofia, Mrak-Poljsak Katjusa, Hinchcliff Monique, Lee Jungwha, Tomsic Matija, Sodin-Semrl Snezna, Varga John
Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.
PLoS One. 2015 Jan 28;10(1):e0110820. doi: 10.1371/journal.pone.0110820. eCollection 2015.
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.
系统性硬化症（SSc）中的炎症是该疾病早期的一个突出但特征尚未完全明确的特征。这些研究的目的是确定炎症标志物急性期蛋白血清淀粉样蛋白A（SAA）在SSc患者中的循环水平、临床相关性及生物学效应。通过多重检测法测定了129例SSc患者和98例健康对照者血清中的SAA循环水平。分析了SAA水平与疾病临床及实验室特征之间的相关性。在体外研究了SAA对人肺成纤维细胞的影响。25%的SSc患者SAA水平升高，其中疾病早期且有弥漫性皮肤受累的患者SAA水平最高。发现SAA与用力肺活量和一氧化碳弥散量呈显著负相关。SAA水平升高的患者呼吸困难更严重，间质性肺疾病更常见，且在患者报告结局指标上得分更差。用重组SAA孵育可诱导培养的正常肺成纤维细胞中IL-6和IL-8呈剂量依赖性刺激。早期弥漫性皮肤型SSc患者炎症标志物SAA的血清水平升高，且与肺部受累相关。在肺成纤维细胞中，SAA可直接刺激细胞因子产生增加。这些发现表明，SSc中的全身炎症可能与肺部受累有关，SAA可能作为这种并发症的潜在生物标志物。
