Rheumatology and Immunology Center, China Medical University Hospital, Taichung; Translational Medicine Laboratory, Rheumatology and Immunology Center, China Medical University Hospital, Taichung, and College of Medicine, China Medical University, Taichung, Taiwan.
Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung; Center for General Education, China Medical University, Taichung, and General Education Center, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
Clin Exp Rheumatol. 2023 May;41(5):1120-1128. doi: 10.55563/clinexprheumatol/int08c. Epub 2022 Oct 4.
Although 1H-nuclear magnetic resonance (NMR)-based lipid/metabolomics has been used to detect atherosclerosis, data regarding lipid/metabolomic signature in rheumatoid arthritis (RA)-related atherosclerosis are scarce. We aimed to identify the distinct lipid/metabolomic profiling and develop a prediction score model for RA patients with subclinical atherosclerosis (SA).
Serum levels of lipid metabolites were determined using 1H-NMR-based lipid/metabolomics in 65 RA patients and 12 healthy controls (HCs). The occurrence of SA was defined as the presence of carotid plaques revealed in ultrasound images.
Compared with HC, RA patients had significantly higher levels of phenylalanine and glycoprotein acetyls (GlycA) and lower levels of leucine and isoleucine. RA patients with SA had significantly higher levels of phenylalanine, creatinine, and glycolysis_total and lower levels of total lipid in HDL(HDL_L) than RA patients without SA. The Lasso logistic regression analysis revealed that age, creatinine, HDL_L, and glycolysis_total were significant predictors for the presence of SA. The prediction scoring algorithm was built as ( -0.657 + 0.011Age + 0.004Creatinine -0.120HDL_L + 0.056glycolysis-related measures), with AUC 0.90, sensitivity 83.3%, and specificity 87.2%. Serum phenylalanine levels were significantly decreased, and the levels of HDL_L and HDL_Particle were significantly increased in 20 RA patients, paralleling the decrease in disease activity score for 28-joints.
With 1H-NMR-based lipid/metabolomics, distinct profiling of lipid metabolites was identified between RA patients and HC or between RA patients with and without SA. We further developed a scoring model based on lipid/metabolomics profiling for predicting RA-associated SA.
尽管基于 1H 核磁共振（NMR）的脂质/代谢组学已被用于检测动脉粥样硬化，但有关类风湿关节炎（RA）相关动脉粥样硬化的脂质/代谢组学特征的数据却很少。我们旨在确定独特的脂质/代谢组学特征，并为患有亚临床动脉粥样硬化（SA）的 RA 患者开发预测评分模型。
使用基于 1H-NMR 的脂质/代谢组学在 65 名 RA 患者和 12 名健康对照者（HCs）中测定脂质代谢产物的血清水平。通过超声图像显示颈动脉斑块来定义 SA 的发生。
与 HC 相比，RA 患者的苯丙氨酸和糖基化乙酰基（GlycA）水平明显升高，亮氨酸和异亮氨酸水平明显降低。与无 SA 的 RA 患者相比，有 SA 的 RA 患者的苯丙氨酸、肌酐和糖酵解总量明显升高，而高密度脂蛋白（HDL_L）中的总脂质水平明显降低。Lasso 逻辑回归分析显示，年龄、肌酐、HDL_L 和糖酵解总量是 SA 存在的显著预测因子。预测评分算法构建为（-0.657+0.011年龄+0.004肌酐-0.120HDL_L+0.056糖酵解相关指标），AUC 为 0.90，敏感性为 83.3%，特异性为 87.2%。20 名 RA 患者的血清苯丙氨酸水平显著降低，HDL_L 和 HDL_Particle 水平显著升高，与 28 关节疾病活动评分的降低相平行。
通过基于 1H-NMR 的脂质/代谢组学，我们在 RA 患者与 HC 之间或在有和无 SA 的 RA 患者之间确定了脂质代谢产物的不同特征。我们进一步基于脂质/代谢组学特征开发了预测 RA 相关 SA 的评分模型。
