类风湿关节炎患者的甘油三酯升高和高密度脂蛋白胆固醇降低的脂质谱：炎症、氧化状态和功能失调的高密度脂蛋白之间的潜在联系。

High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein.

机构信息

Area of Immunology, Department of Functional Biology, University of Oviedo, Asturias, Spain.

Department of Rheumatology, Hospital Universitario Central de Asturias, Asturias, Spain.

出版信息

J Clin Lipidol. 2017 Jul-Aug;11(4):1043-1054.e2. doi: 10.1016/j.jacl.2017.05.009. Epub 2017 Jun 3.

DOI:10.1016/j.jacl.2017.05.009

PMID:28662934

Abstract

BACKGROUND

The interactions between inflammation and lipid profile in rheumatoid arthritis (RA) are poorly understood. The lipid profile study in RA has been biased toward lipoprotein levels, whereas those of triglycerides (TGs) and lipoprotein functionality have been underestimated.

OBJECTIVES

Since recent findings suggest a role for TG and TG-rich lipoproteins (TRL) on inflammation, we aimed to evaluate a combined lipid profile characterized by high TG and low high-density lipoprotein cholesterol levels (TGHDL) in RA.

METHODS

Lipid profiles were analyzed in 113 RA patients, 113 healthy controls, and 27 dyslipemic subjects. Levels of inflammatory mediators, paraoxonase-1 (PON1) activity, and total antioxidant capacity were quantified in serum. PON1-rs662 status was evaluated by real-time polymerase chain reaction.

RESULTS

The TGHDL profile was detected in 29/113 RA patients. Although no differences in prevalence compared with healthy controls or dyslipemic subjects were observed, this profile was associated with increased tumor necrosis factor α (P = .004), monocyte chemotactic protein (P = .004), interferon-gamma-inducible protein-10 (P = .018), and leptin (P < .001) serum levels in RA, where decreased PON1 activity and total antioxidant capacity were found. TGHDL prevalence was lower among anti-TNFα-treated patients (P = .004). When RA patients were stratified by PON1-rs662 status, these associations remained in the low-activity genotype (QQ). Finally, a poor clinical response on TNFα blockade was related to an increasing prevalence of the TGHDL profile over treatment (P = .021) and higher TRL levels at baseline (P = .042).

CONCLUSIONS

The TGHDL profile is associated with systemic inflammation, decreased PON1 activity, and poor clinical outcome on TNFα blockade in RA, suggesting a role of TRL and HDL dysfunction as the missing link between inflammation and lipid profile.

摘要

背景

类风湿关节炎（RA）中炎症与血脂谱之间的相互作用尚不清楚。RA 的血脂谱研究偏向于脂蛋白水平，而对甘油三酯（TG）和脂蛋白功能的研究则被低估了。

目的

由于最近的研究结果表明 TG 和富含 TG 的脂蛋白（TRL）在炎症中起作用，我们旨在评估 RA 中具有高 TG 和低高密度脂蛋白胆固醇水平（TGHDL）特征的综合血脂谱。

方法

分析了 113 例 RA 患者、113 例健康对照者和 27 例血脂异常患者的血脂谱。检测血清中炎症介质、对氧磷酶-1（PON1）活性和总抗氧化能力的水平。通过实时聚合酶链反应评估 PON1-rs662 状态。

结果

在 113 例 RA 患者中检测到 TGHDL 谱。尽管与健康对照者或血脂异常患者相比，该谱的患病率没有差异，但在 RA 患者中，该谱与肿瘤坏死因子-α（P=0.004）、单核细胞趋化蛋白（P=0.004）、干扰素-γ诱导蛋白-10（P=0.018）和瘦素（P<0.001）血清水平升高相关，同时发现 PON1 活性和总抗氧化能力降低。接受 TNFα 治疗的患者中 TGHDL 的患病率较低（P=0.004）。当根据 PON1-rs662 状态对 RA 患者进行分层时，这些关联在低活性基因型（QQ）中仍然存在。最后，TNFα 阻断的临床反应较差与治疗过程中 TGHDL 谱的患病率增加（P=0.021）和基线时 TRL 水平升高（P=0.042）有关。