Fiocco Ugo, Oliviero Francesca, Sfriso Paolo, Calabrese Fiorella, Lunardi Francesca, Scagliori Elena, Rubaltelli Leopoldo, Stramare Roberto, Di Maggio Antonio, Nardacchione Roberto, Cozzi Luisella, Molena Beatrice, Felicetti Mara, Gazzola Katia, Lo Nigro Alessandro, Accordi Benedetta, Roux-Lombard Pascale, Dayer Jean-Michel, Punzi Leonardo
Department of Medicine, University of Padua, Padua, Italy.
J Rheumatol Suppl. 2012 Jul;89:61-4. doi: 10.3899/jrheum.120246.
To find candidate biomarkers of psoriatic arthritis (PsA). A panel of synovial fluid (SF) and synovial tissue (ST) biomarkers was analyzed in patients with resistant peripheral PsA, in relation to clinical and imaging outcomes of synovitis response following serial intraarticular (IA) etanercept injections (12.5 mg).
Fourteen PsA patients with resistant knee joint synovitis were treated with 4 IA etanercept injections in a single knee joint, once every 2 weeks. Primary outcome (Thompson's knee index: THOMP) and secondary outcomes were assessed at baseline and end of study: C-reactive protein, Knee Joint Articular Index (KJAI), Health Assessment Questionnaire disability index, maximal synovial thickness (MST) by gray-scale ultrasonography, contrast-enhanced magnetic resonance imaging (C+MRI), ST-cluster differentiation (CD)45+ mononuclear cell, ST-CD31+ vessels, and ST-CD105+ angiogenic endothelial cells, along with levels of SF interleukin 1ß (IL-1ß), IL-1 receptor antagonist (Ra), and IL-6.
At the end of the study, clinical and imaging outcomes, ST and SF biological markers were significantly reduced compared to baseline. There was a significant association between IL-6 and either THOMP or KJAI; between either ST-CD31+ or ST-CD105+ or ST-CD45+; between ST and SF biomarkers expression (CD45+ and IL-1ß) and between ST-CD45+ and both KJAI and MRI-MST. Comparing pre- versus post-IA etanercept injection changes (Δ), Δ IL-1ß was significantly correlated with both Δ IL-6 and with Δ IL-1Ra and Δ IL-6 with Δ IL-1Ra.
The association to disease activity and the changes following IA treatment indicate that ST-CD45+ and ST-CD31+, along with SF-IL-6 and SF-IL-1ß, may represent candidate biomarkers of the knee synovitis response to IA tumor necrosis factor-α blockade.
寻找银屑病关节炎(PsA)的候选生物标志物。对难治性外周PsA患者的一组滑液(SF)和滑膜组织(ST)生物标志物进行分析,分析其与连续关节内(IA)注射依那西普(12.5mg)后滑膜炎反应的临床和影像学结果的关系。
14例难治性膝关节滑膜炎的PsA患者在单膝关节接受4次IA依那西普注射,每2周1次。在基线和研究结束时评估主要结局(汤普森膝关节指数:THOMP)和次要结局:C反应蛋白、膝关节关节指数(KJAI)、健康评估问卷残疾指数、灰阶超声检查的最大滑膜厚度(MST)、对比增强磁共振成像(C+MRI)、ST-簇分化(CD)45+单核细胞、ST-CD31+血管和ST-CD105+血管生成内皮细胞,以及SF白细胞介素1β(IL-1β)、IL-1受体拮抗剂(Ra)和IL-6水平。
研究结束时,与基线相比,临床和影像学结果、ST和SF生物标志物显著降低。IL-6与THOMP或KJAI之间存在显著关联;ST-CD31+或ST-CD105+或ST-CD45+之间存在显著关联;ST和SF生物标志物表达(CD45+和IL-1β)之间以及ST-CD45+与KJAI和MRI-MST之间存在显著关联。比较IA依那西普注射前后的变化(Δ),ΔIL-1β与ΔIL-6以及ΔIL-1Ra均显著相关,ΔIL-6与ΔIL-1Ra也显著相关。
与疾病活动的关联以及IA治疗后的变化表明,ST-CD45+和ST-CD31+,以及SF-IL-6和SF-IL-1β,可能代表膝关节滑膜炎对IA肿瘤坏死因子-α阻断反应的候选生物标志物。