Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Sci Rep. 2020 Dec 3;10(1):21094. doi: 10.1038/s41598-020-78204-6.
Spondyloarthritis (SpA) is characterized by inflammation and new bone formation. The exact pathophysiology underlying these processes remains elusive. We propose that the extensive neoangiogenesis in SpA could play a role both in sustaining/enhancing inflammation and in new bone formation. While ample data is available on effects of anti-TNF on angiogenesis, effects of IL-17A blockade on serum markers are largely unknown. We aimed to assess the impact of secukinumab (anti-IL-17A) on synovial neoangiogenesis in peripheral SpA, and how this related to changes in inflammatory and tissue remodeling biomarkers. Serum samples from 20 active peripheral SpA patients included in a 12 week open-label trial with secukinumab were analyzed for several markers of angiogenesis and tissue remodeling. Synovial biopsies taken before and after treatment were stained for vascular markers. Serum levels of MMP-3, osteopontin, IL-6 (all P < 0.001), IL-31, S100A8, S100A9, Vascular Endothelial Growth Factor A (VEGF-A), IL-33, TNF-α (all P < 0.05) decreased significantly upon anti-IL17A treatment. Secukinumab treatment resulted in a decrease in the number of synovial high endothelial venules and lymphoid aggregate score. These results indicate that anti-IL-17A not only diminishes inflammation, but also impacts angiogenesis and tissue remodeling/new bone formation. This may have important implications for disease progression and/or structural damage.
脊柱关节炎(SpA)的特征是炎症和新骨形成。这些过程的确切病理生理学仍然难以捉摸。我们提出,SpA 中的广泛新生血管形成可能在维持/增强炎症和新骨形成中发挥作用。虽然有大量关于抗 TNF 对血管生成影响的数据,但关于 IL-17A 阻断对血清标志物影响的数据在很大程度上尚不清楚。我们旨在评估 secukinumab(抗 IL-17A)对周围性 SpA 滑膜新生血管形成的影响,以及这与炎症和组织重塑生物标志物变化的关系。在一项为期 12 周的 secukinumab 开放标签试验中纳入的 20 例活动性周围性 SpA 患者的血清样本用于分析几种血管生成和组织重塑标志物。在治疗前后采集滑膜活检标本,用于血管标志物染色。基质金属蛋白酶 3(MMP-3)、骨桥蛋白、白细胞介素 6(均 P<0.001)、白细胞介素 31、S100A8、S100A9、血管内皮生长因子 A(VEGF-A)、白细胞介素 33、肿瘤坏死因子-α(均 P<0.05)的血清水平在抗 IL17A 治疗后显著降低。secukinumab 治疗导致滑膜高内皮静脉和淋巴聚集评分的数量减少。这些结果表明,抗 IL-17A 不仅可减轻炎症,还可影响血管生成和组织重塑/新骨形成。这可能对疾病进展和/或结构损伤有重要意义。