A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients.
A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients.
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DOI：
10.1136/annrheumdis-2013-203622
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发表时间：
2014-06
影响因子：
27.4
通讯作者：
Pierangeli SS
中科院分区：
文献类型：
--
作者：
Erkan D;Willis R;Murthy VL;Basra G;Vega J;Ruiz-Limón P;Carrera AL;Papalardo E;Martínez-Martínez LA;González EB;Pierangeli SS
目的：确定抗磷脂抗体(APL)持续阳性患者的促炎和促血栓生物标记物是否有差异上调，并检测氟伐他汀对这些生物标记物的影响。4组患者(年龄18~65岁)：a)原发性抗磷脂综合征(PAPS)；b)系统性红斑狼疮(SLE)合并APS(SLE/APS)；c)APL持续阳性不伴SLE或APS(原发APL)；d)持续APL阳性伴SLE但无APS(SLE/APL)。频率匹配的对照组，用于基线数据比较，从健康人的数据库中确定。患者每日服用氟伐他汀40 mg，连续3个月。三个月后，患者停止研究药物治疗，并继续跟踪治疗三个月。连续6个月每月采集12个促炎症和促血栓生物标志物的血样。41例急性早幼粒细胞白血病阳性患者与30例健康体检者比较，9/12(75%)的细胞因子(IL-6、IL-1β、血管内皮生长因子、肿瘤坏死因子-α、干扰素-α、诱导蛋白-10、可溶性CD40L、可溶性组织因子、细胞间黏附分子-1)明显升高。24名患者完成了这项研究；氟伐他汀显著且可逆地降低了6/12(50%)生物标记物的水平(白介素1β、血管内皮生长因子、肿瘤坏死因子α、IP10、sCD40L和STF)。我们的前瞻性机制研究表明，在APL持续阳性患者中差异表达的促炎和促血栓生物标志物可以被氟伐他汀可逆地降低。因此，他汀类药物诱导的对靶细胞的APL效应的调节在APL阳性患者的治疗中是一种有价值的未来方法。
To determine if pro-inflammatory and pro-thrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Four groups of patients (age 18-65) were recruited: a) Primary Antiphospholipid Syndrome (PAPS); b) Systemic Lupus Erythematosus (SLE) with APS (SLE/APS); c) Persistent aPL positivity without SLE or APS (Primary aPL); and d) Persistent aPL positivity with SLE but no APS (SLE/aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for three months. At three months, patients stopped the study medication and they were followed for another three months. Blood samples for 12 pro-inflammatory and pro-thrombotic biomarkers were collected monthly for six months. Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin [IL]-6, IL1β, vascular endothelial growth factor [VEGF], tumor necrosis factor [TNF]-□α, interferon [IFN]-α, inducible protein-10 [IP10], soluble CD40 ligand [sCD40L], soluble tissue factor [sTF], and intracellular cellular adhesion molecule [ICAM]-1) were significantly elevated. Twenty-four patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L, and sTF). Our prospective mechanistic study demonstrates that pro-inflammatory and pro-thrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients.