ARD：利妥昔单抗治疗可降低RA患者血清致动脉粥样硬化脂蛋白

致动脉粥样硬化血脂是心血管疾病（CV）的确定风险因素，而类风湿关节炎（CV）的高炎状态与不良血脂相关。新的免疫调节药物如利妥昔单抗（RTX）对血脂作用的数据有限。来自荷兰阿姆斯特丹UV大学医学中心的Hennie G Raterman等人对RTX治疗RA后患者血脂的变化进行了评估。研究结果发表在2013年4月的《风湿病学年鉴》（Ann Rheum Dis）杂志上。结果表明，RTX在改善疾病活动度的同时，对血脂也有益处。
对49例连续应用RTX的RA患者进行评估，分别在基线时、1月、3月及6月时收集血清和EDTA血浆样本，并对样本中的血脂种类和水平改变及时进行评估。用表面增强激光解吸电离飞行时间质谱（SELDI-TOF MS）技术对6例治疗反应良好和6例无治疗反应的RA患者的功能性高密度脂蛋白（HDL）组成变化进行及时研究。
在总组（49例）中，6个月后，致动脉粥样硬化指数从4.3下降到3.9（~9%）。效应修饰检测结果显示，对RTX有治疗反应和无治疗反应的患者其脂蛋白水平存在显著差异（p<0.001）。在治疗反应良好的32例患者中，ApoB 比ApoA-I的比例明显下降（~9%）。SELDI-TOF MS检测显示，在治疗反应良好的患者中，质荷比（m/z）密度标记11743明显下降，提示血清淀粉蛋白A的降低。
研究表明，RTX在改善疾病活动度的同时，对血脂也有益处。蛋白质组学分析揭示，在6个月的RTX治疗期间，HDL颗粒组成中致粥样硬化成分更少。免疫治疗期间HDL颗粒的改变是否可以降低CV的发生率仍需进一步确认。
与动脉粥样硬化相关的拓展阅读：

• Diabetes Care：T1DM增加青年动脉粥样硬化风险
• J Psychiatr Res：初诊抑郁症与动脉粥样硬化相关
• Diabetes Care：T1DM患者维生素D代谢受损与动脉粥样硬化没有相关性
• Diabetes Care：甘精胰岛素轻度降低动脉粥样硬化风险
• EMBO：揭示单核细胞迁移至血管壁导致动脉粥样硬化机制
• J BIOL CHEM:发现抑制动脉粥样硬化新分子信号途径
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HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab.
OBJECTIVE
An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid profile are limited. Therefore, changes in lipids in RTX treated RA patients were evaluated.
METHODS
In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time.
RESULTS
In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (∼9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (∼9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients.
CONCLUSION
This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.