Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Weill Medical College of Cornell University, , New York, NY, USA.
Ann Rheum Dis. 2014 Jun;73(6):1176-80. doi: 10.1136/annrheumdis-2013-203622. Epub 2013 Aug 9.
To determine if proinflammatory and prothrombotic 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; (b) systemic lupus erythematosus (SLE) with antiphospholipid syndrome (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 3 months. At 3 months, patients stopped the study medication and they were followed for another 3 months. Blood samples for 12 proinflammatory and prothrombotic biomarkers were collected monthly for 6 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), tumour 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 proinflammatory and prothrombotic 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.
确定持续性抗磷脂抗体（aPL）阳性患者中促炎和促血栓形成生物标志物是否存在差异上调，并研究氟伐他汀对这些生物标志物的影响。
招募了四组患者（年龄 18-65 岁）：（a）原发性抗磷脂综合征；（b）系统性红斑狼疮（SLE）伴抗磷脂综合征（APS）（SLE/APS）；（c）持续性 aPL 阳性但无 SLE 或 APS（原发性 aPL）；和（d）持续性 aPL 阳性伴 SLE 但无 APS（SLE/aPL）。从健康人群的数据库中确定了与对照组频率匹配的对照组，用于基线数据比较。患者每日接受氟伐他汀 40mg 治疗 3 个月。3 个月时，患者停止研究药物治疗，并再随访 3 个月。在 6 个月内每月采集 12 种促炎和促血栓形成生物标志物的血液样本。
基于对 41 例 aPL 阳性患者和 30 例健康对照者的基线样本比较，9/12（75%）生物标志物（白细胞介素（IL）-6、IL1β、血管内皮生长因子（VEGF）、肿瘤坏死因子（TNF）-α、干扰素（IFN）-α、诱导蛋白-10（IP10）、可溶性 CD40 配体（sCD40L）、可溶性组织因子（sTF）和细胞间黏附分子（ICAM）-1）显著升高。24 例患者完成了研究；氟伐他汀可显著且可逆地降低 6/12（50%）生物标志物（IL1β、VEGF、TNFα、IP10、sCD40L 和 sTF）的水平。
我们的前瞻性机制研究表明，持续性 aPL 阳性患者中存在差异上调的促炎和促血栓形成生物标志物可被氟伐他汀可逆性降低。因此，他汀类药物对 aPL 作用于靶细胞的调节作用可能是治疗 aPL 阳性患者的一种有价值的未来方法。
