纤溶酶-α2-纤维蛋白溶酶抑制剂复合物可预测环磷酰胺对硬皮病相关间质性肺病疗效

作者：Saigusa R, et al.

翻译：金银姬 ，校对：武东

摘要：目的：静脉冲击环磷酰胺 (IVCY) 是治疗系统性硬化症相关间质性肺病(SSc-ILD)的一线治疗。到目前为止，尽管反映血管活化的参数可潜在预测其疗效，但还没有预测IVCY对SSc-ILD疗效的有效指标。因纤溶酶-α2-纤维蛋白溶酶抑制剂复合物（PIC）可能为系统性硬化症患者血管病变的一种潜在生物标志物，我们评估了血浆PIC水平作为IVCY对SSc-ILD疗效。

方法：我们纳入23名活动性SSc-ILD患者及20名病情平稳的SSc-ILD患者，检测患者血浆PIC水平，同时回顾性分析IVCY治疗期间活动性SSc-ILD患者的临床数据。

结果：活动性SSc-ILD患者较稳定的SSc-ILD相比，血浆PIC水平显著升高。活动性SSc-ILD患者中，对IVCY反应好的患者基线血浆PIC浓度显著高于对IVCY反应欠佳的患者。6个月治疗后，血浆PIC水平在IVCY反应好的患者中较基线显著下降，但在反应欠佳的患者中无差异。在前者，血浆PIC水平在输注几次后显著下降。考虑到整个注射过程中参数变化，Δ血浆PIC水平与Δ血清KL-6水平正相关，与预测肺活量百分比负相关。

结论：基线血浆PIC水平升高及环磷酰胺冲击后血浆PIC的显著下降可预测整个环磷酰胺冲击治疗对SSc-ILD的疗效。

附原文：Abstract OBJECTIVES:Intravenous pulse cyclophosphamide (IVCY) is the first-line treatment for systemic sclerosis-associated interstitial lung disease (SSc-ILD). So far, there is no useful predictive marker for IVCY efficacy against SSc-ILD, although potential candidates are parameters reflecting vascular activation. Since plasma levels of plasmin-α2-plasmin inhibitor complex (PIC) serve as a potential biomarker of SSc vasculopathy, we evaluated the usefulness of plasma PIC levels as an indicator for IVCY efficacy against SSc-ILD. METHODS:We measured plasma PIC levels in 23 patients with active SSc-ILD and 20 patients with stabilized SSc-ILD, and also retrospectively studied traceable data of patients with active SSc-ILD during IVCY therapy. RESULTS:Plasma PIC levels were significantly elevated in patients with active SSc-ILD as compared to patients with stabilized SSc-ILD. Among patients with active SSc-ILD, baseline plasma PIC concentrations were significantly higher in patients responsive to IVCY than in those refractory to IVCY. After the entire 6 infusions, plasma PIC levels were significantly decreased compared with baseline in the responders, while not in the non-responders. In the responders, plasma PIC levels were remarkably decreased after a couple of infusions. Regarding the changes of parameters by the entire infusions, Δ plasma PIC levels correlated positively with Δ serum KL-6 levels and inversely with Δ the percentage of predicted vital capacity. CONCLUSIONS:The elevation of baseline plasma PIC levels and the rapid decrease in plasma PIC levels during a couple of infusions may predict the efficacy of the entire IVCY therapy against SSc-ILD.

引自：Saigusa R, Asano Y, Nakamura K, et al. Plasma plasmin-α2-plasmin inhibitor complex levels may predict the effect of cyclophosphamide for systemic sclerosis-related interstitial lung disease. Mod Rheumatol. 2016 Aug 19:1-14. [Epub ahead of print]