Rodríguez-Carrio Javier, Alperi-López Mercedes, López Patricia, Ballina-García Francisco J, Abal Francisco, Suárez Ana
Area of Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Asturias, Spain.
Department of Rheumatology, Hospital Universitario Central de Asturias, Oviedo, Spain.
Transl Res. 2015 Dec;166(6):529-39. doi: 10.1016/j.trsl.2015.07.004. Epub 2015 Jul 30.
Several lines of evidence suggest that chronic inflammation and immune dysregulation are related to altered lipid profiles in rheumatoid arthritis (RA), but the actual mechanisms are still unclear. We wondered whether the development of antibodies against high-density lipoprotein (HDL) can be found in RA patients linked to clinical and cardiovascular (CV) risk factors. To this end, immunoglobulin G (IgG) anti-HDL antibodies and total IgG serum levels were quantified in 212 RA patients, 131 sex- and age-matched healthy controls (HC), and 52 subjects with traditional CV risk factors (tCVRs). A subgroup of 13 RA patients was prospectively followed on TNFα-blockade. TNFα, interferon (IFN)α, MIP1α, IFNγ, IL-8, VEGF, GM-CSF, IL-17, MCP-1, SDF-1α, resistin, and leptin serum levels were quantified by immunoassays. IgG anti-HDL levels were higher in RA patients compared with HC (P < 0.0001) and tCVR subjects (P = 0.015). Differences with HC remained after correction for total IgG levels (P < 0.003). Anti-HDL/IgG were negatively associated with HDL levels in RA (-1.182 [-1.823 to -0.541], P = 0.0003) after adjusting for demographical, clinical, inflammatory parameters, and treatments. RA patients with high levels of anti-HDL/IgG (n = 40, 18.8%) were more likely to have experienced a CV event (P < 0.0001) and exhibited increased levels of several proinflammatory mediators (C-reactive protein, IFNα, MIP1α, IFNγ, IL-8, GM-CSF, IL-17 and MCP-1). Finally, change in anti-HDL antibodies on TNFα-blockade was independently associated with increasing HDL levels. Overall, IgG anti-HDL antibodies are increased in RA independently of tCVRs and associated with a proinflammatory milieu and impaired lipid blood profile, which may contribute to the increased rate of CV events in these patients.
多项证据表明，慢性炎症和免疫失调与类风湿关节炎（RA）患者血脂谱改变有关，但具体机制仍不清楚。我们想知道，在RA患者中是否能发现抗高密度脂蛋白（HDL）抗体的产生与临床及心血管（CV）危险因素有关。为此，我们对212例RA患者、131例性别和年龄匹配的健康对照者（HC）以及52例具有传统CV危险因素（tCVR）的受试者进行了免疫球蛋白G（IgG）抗HDL抗体和总IgG血清水平的定量检测。对13例RA患者的亚组进行了TNFα阻断治疗的前瞻性随访。通过免疫测定法定量检测TNFα、干扰素（IFN）α、MIP1α、IFNγ、IL - 8、VEGF、GM - CSF、IL - 17、MCP - 1、SDF - 1α、抵抗素和瘦素的血清水平。与HC相比，RA患者的IgG抗HDL水平更高（P < 0.0001），与tCVR受试者相比也更高（P = 0.015）。校正总IgG水平后，与HC的差异仍然存在（P < 0.003）。在调整了人口统计学、临床、炎症参数和治疗因素后，RA患者中抗HDL/IgG与HDL水平呈负相关（-1.182 [-1.823至-0.541]，P = 0.0003）。抗HDL/IgG水平高的RA患者（n = 40，18.8%）更有可能发生CV事件（P < 0.0001），并且几种促炎介质（C反应蛋白、IFNα、MIP1α、IFNγ、IL - 8、GM - CSF、IL - 十七和MCP - 1）水平升高。最后，TNFα阻断治疗后抗HDL抗体的变化与HDL水平升高独立相关。总体而言，RA患者中IgG抗HDL抗体升高，独立于tCVR，且与促炎环境和血脂谱受损有关这可能导致这些患者CV事件发生率增加。
