Šumová Barbora, Cerezo Lucie Andrés, Hulejová Hana, Prajzlerová Klára, Tomčík Michal, Bubová Kristýna, Štěpán Jan, Filková Mária, Kropáčková Tereza, Grigorian Mariam, Pavelka Karel, Vencovský Jiří, Šenolt Ladislav
1Institute of Rheumatology, Prague, Czech Republic.
2Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
BMC Rheumatol. 2020 Jan 31;4:13. doi: 10.1186/s41927-019-0110-7. eCollection 2020.
S100A4 is a member of calcium binding S100 protein family well known for its role in cancer progression and metastasis. Nevertheless, S100A4 also serves as a negative regulator of bone formation. Dickkopf-1 (DKK-1), marker of bone remodelling, is also implicated in the process of syndesmophyte formation in ankylosing spondylitis. The aim of our study was to evaluate plasma levels of S100A4 in patients with axial spondyloarthritis and to determine the potential association of S100A4 with disease severity, clinical manifestations and with bone changes in a cross-sectional study.
Fifty-eight patients with axial spondyloarthritis and 40 healthy controls were studied. Biological samples were analysed for S100A4 and Dickkopf-1. Disease activity was assessed according to the Bath Ankylosing Spondylitis Disease Activity Index. C-reactive protein (CRP) was used as a marker of inflammation. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).
The plasma levels of S100A4 were significantly higher in patients with axial spondyloarthritis compared to heathy controls ( < 0.0001). The levels of S100A4 were higher in early stages of the disease and lower in patients with the presence of syndesmophytes ( = 0.009). Furthermore, we found weak but significant inverse correlation of plasma S100A4 with the mSASSS (r = - 0.363, = 0.030). Levels of S100A4 were negatively associated with disease duration (r = - 0.404, = 0.002) and positively with Dickkopf-1 binding capacity (r = 0.312, = 0.023).
This is the first study showing elevated circulating levels of S100A4 in patients with axial spondyloarthritis, particularly in early stages of the disease prior to spinal involvement, and its significantly lower levels in patients with syndesmophytes. The role of S100A4 in the pathogenesis of axial spondyloarthritis can be suggested.
S100A4是钙结合S100蛋白家族的成员，因其在癌症进展和转移中的作用而闻名。然而，S100A4也作为骨形成的负调节因子。骨重塑标志物Dickkopf-1（DKK-1）也与强直性脊柱炎中韧带骨赘的形成过程有关。我们研究的目的是在一项横断面研究中评估轴性脊柱关节炎患者的血浆S100A4水平，并确定S100A4与疾病严重程度、临床表现以及骨改变之间的潜在关联。
研究了58例轴性脊柱关节炎患者和40例健康对照者。对生物样本进行S100A4和Dickkopf-1分析。根据巴斯强直性脊柱炎疾病活动指数评估疾病活动度。使用C反应蛋白（CRP）作为炎症标志物。采用改良斯托克强直性脊柱炎脊柱评分（mSASSS）评估影像学损伤。
与健康对照者相比，轴性脊柱关节炎患者的血浆S100A4水平显著更高（<0.0001）。S100A4水平在疾病早期较高，在有韧带骨赘的患者中较低（=0.009）。此外，我们发现血浆S100A4与mSASSS呈弱但显著的负相关（r=-0.363，=0.030）。S100A4水平与疾病持续时间呈负相关（r=-0.404，=0.002），与Dickkopf-1结合能力呈正相关（r=0.312，=0.023）。
这是第一项显示轴性脊柱关节炎患者循环S100A4水平升高的研究，特别是在脊柱受累之前的疾病早期，而在有韧带骨赘的患者中其水平显著更低。可以推测S100A4在轴性脊柱关节炎发病机制中的作用。
