State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, People's Republic of China.
Arthritis Res Ther. 2011 Feb 8;13(1):R17. doi: 10.1186/ar3241.
Follistatin-like protein 1 (FSTL1) is a proinflammation mediator implicated in arthritis in rodent animal models. The present study is aimed at assessing FSTL1 levels in systemic autoimmune diseases and correlating them with disease activity in patients with rheumatoid arthritis (RA).
Serum FSTL1 levels from 487 patients with systemic autoimmune diseases and 69 healthy individuals were measured by enzyme-linked immunosorbent assay (ELISA). FSTL1 expression in synovial fluid (SF) and synovial tissues (STs) was determined by ELISA, immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and western blot analysis in RA patients and trauma controls. FSTL1 levels in fibroblast-like synoviocytes (FLSs) from RA patients were determined by real-time PCR and western blot analysis.
Serum FSTL1 levels were significantly elevated in patients with RA, ulcerative colitis, systemic lupus erythematosus, Sjögren's syndrome (SS), systemic sclerosis and polymyositis/dermatomyositis. Serum FSTL1 levels in the RA and secondary SS patients were substantially higher than those in other patients. Serum FSTL1 levels were increased in early RA, rheumatoid factor (RF)- and anti-cyclic citrullinated peptide antibody (ACPA)-negative patients compared to healthy controls. Moreover, serum FSTL1 concentrations were significantly higher in long-standing RA patients than in early RA patients and in the RF- and ACPA-positive RA patients than in RF- and ACPA-negative RA patients. Elevated FSTL1 levels in the STs and SF of RA patients were also observed. FSTL1 levels in serum were markedly higher than those in SF in RA patients. The strongest FSTL1 staining was detected in the cytoplasm of synovial and capillary endothelial cells from RA synovium. Furthermore, FSTL1 was induced in FLSs by inflammatory mediators. Importantly, serum FSTL1 levels were correlated with several important biologic and clinical markers of disease activity, including erythrocyte sedimentation rate, C-reactive protein, RF, ACPA, swollen joint count, patient global visual analogue scale score and Disease Activity Score 28 in the adult RA patient population. Notably, serum FSTL1 levels were significantly diminished following successful treatment and clinical improvement.
Elevated FSTL1 levels reflect not only joint diseases but also inflammation and tissue degradation in systemic autoimmune diseases. Serum FSTL1 levels may thus serve as a serological inflammatory marker of disease activity in RA patients.
卵泡抑素样蛋白 1（Follistatin-like protein 1，FSTL1）是一种促炎介质，在啮齿动物关节炎模型中与关节炎有关。本研究旨在评估系统性自身免疫性疾病患者的 FSTL1 水平，并与类风湿关节炎（rheumatoid arthritis，RA）患者的疾病活动度相关联。
采用酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）检测 487 例系统性自身免疫性疾病患者和 69 例健康个体的血清 FSTL1 水平。采用 ELISA、免疫组化、实时聚合酶链反应（real-time polymerase chain reaction，RT-PCR）和 Western blot 分析 RA 患者和创伤对照的滑膜液（synovial fluid，SF）和滑膜组织（synovial tissues，STs）中 FSTL1 的表达。采用实时 PCR 和 Western blot 分析 RA 患者成纤维样滑膜细胞（fibroblast-like synoviocytes，FLSs）中的 FSTL1 水平。
RA、溃疡性结肠炎、系统性红斑狼疮、干燥综合征、系统性硬皮病和多发性肌炎/皮肌炎患者的血清 FSTL1 水平显著升高。RA 和继发性干燥综合征患者的血清 FSTL1 水平明显高于其他患者。与健康对照组相比，早期 RA、类风湿因子（rheumatoid factor，RF）和抗环瓜氨酸肽抗体（anti-cyclic citrullinated peptide antibody，ACPA）阴性患者的血清 FSTL1 水平升高。此外，与早期 RA 患者和 RF 和 ACPA 阳性 RA 患者相比，长期 RA 患者的血清 FSTL1 浓度明显更高。RA 患者的 ST 和 SF 中也观察到 FSTL1 水平升高。RA 患者血清中的 FSTL1 水平明显高于 SF 中的 FSTL1 水平。RA 滑膜中滑膜细胞和毛细血管内皮细胞的细胞质中检测到最强的 FSTL1 染色。此外，炎症介质可诱导 FLSs 产生 FSTL1。重要的是，血清 FSTL1 水平与成人 RA 患者人群中疾病活动的几个重要生物学和临床标志物相关，包括红细胞沉降率、C 反应蛋白、RF、ACPA、肿胀关节计数、患者总体视觉模拟评分和 28 个关节疾病活动度评分。值得注意的是，在成功治疗和临床改善后，血清 FSTL1 水平显著降低。
升高的 FSTL1 水平不仅反映关节疾病，还反映系统性自身免疫性疾病中的炎症和组织降解。因此，血清 FSTL1 水平可作为 RA 患者疾病活动的血清炎症标志物。
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