IgM 抗磷酰胆碱抗体与 SLE 患者中具有促炎脂质特征的衰老和 IL-17+T 细胞相关。
IgM anti-phosphorylcholine antibodies associate with senescent and IL-17+ T cells in SLE patients with a pro-inflammatory lipid profile.
机构信息
Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo.
Group of Basic and Translational Research in Inflammatory Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA).
出版信息
Rheumatology (Oxford). 2020 Feb 1;59(2):407-417. doi: 10.1093/rheumatology/kez264.
OBJECTIVE
The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE.
METHODS
Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. Carotid atheromatosis was evaluated by ultrasonography; Th1, Th17, Treg and CD4+CD28null cells by flow cytometry; and cytokine serum levels by immunoassays, in a subgroup of 120 SLE patients and 33 controls.
RESULTS
IgM anti-PC serum levels were reduced in SLE patients compared with controls (P < 0.001) and were associated with age (β= -0.252; P = 0.002), high-density lipoprotein (HDL; β = 0.271; P = 0.001), low-density lipoprotein (LDL; β= -0.192; P = 0.017) and glucocorticoid treatment (β= -0.201; P = 0.012), whereas the IgG-to-IgM anti-PC ratio was increased (P = 0.007) and associated with age (β = 0.194; P = 0.028) and SLEDAI (β = 0.250; P = 0.005). Also, patients with clinical or subclinical cardiovascular disease exhibited reduced IgM anti-PC levels compared with their cardiovascular disease-free counterparts, regardless of glucocorticoid usage (P = 0.001). CD4+CD28null and Th17 cells were increased in SLE patients compared with controls (P < 0.01) and correlated inversely with IgM anti-PC levels. These associations were observed in patients displaying high triglyceride or low HDL levels, even after adjusting for clinical parameters and treatments (CD4+CD28null: β = -0.455, P = 0.001; Th17: β= -0.280, P = 0.035), but not in those with a normal lipid profile. High triglyceride and low HDL profiles were related to low IgM anti-PC and Treg levels, respectively, whereas both lipid profiles were associated with inflammatory markers and cytokines.
CONCLUSION
The present study provides evidence for an association of IgM anti-PC antibodies with pro-atherogenic T cell subsets in SLE, with a high triglyceride/low HDL lipid profile playing a facilitating major role.
目的
评估 T 细胞亚群和脂谱是否与 SLE 中 IgM 抗磷酰胆碱（PC）抗体的心脏保护作用有关。
方法
通过 ELISA 在 197 例患者和 99 例对照中定量测定抗 PC 抗体，并分析与临床特征、治疗和血清脂质的关系。通过超声检查评估颈动脉粥样硬化；通过流式细胞术评估 Th1、Th17、Treg 和 CD4+CD28null 细胞；通过免疫分析评估亚组 120 例 SLE 患者和 33 例对照的细胞因子血清水平。
结果
与对照组相比，SLE 患者的 IgM 抗 PC 血清水平降低（P < 0.001），与年龄（β=-0.252；P=0.002）、高密度脂蛋白（HDL；β=0.271；P=0.001）、低密度脂蛋白（LDL；β=-0.192；P=0.017）和糖皮质激素治疗（β=-0.201；P=0.012）相关，而 IgG 与 IgM 抗 PC 比值升高（P=0.007），与年龄（β=0.194；P=0.028）和 SLEDAI（β=0.250；P=0.005）相关。此外，无论是否使用糖皮质激素，有临床或亚临床心血管疾病的患者的 IgM 抗 PC 水平均低于无心血管疾病的患者（P=0.001）。与对照组相比，SLE 患者的 CD4+CD28null 和 Th17 细胞增加（P < 0.01），并与 IgM 抗 PC 水平呈负相关。这些关联在高甘油三酯或低 HDL 水平的患者中观察到，即使在调整临床参数和治疗后（CD4+CD28null：β=-0.455，P=0.001；Th17：β=-0.280，P=0.035），但在血脂正常的患者中未观察到。高甘油三酯和低 HDL 谱分别与低 IgM 抗 PC 和 Treg 水平相关，而两种脂质谱均与炎症标志物和细胞因子相关。
结论
本研究提供了 SLE 中 IgM 抗 PC 抗体与促动脉粥样硬化 T 细胞亚群相关的证据，高甘油三酯/低 HDL 脂质谱起着促进的主要作用。
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