Rheumatology and Immunology Center, China Medical University Hospital, Taichung 404, Taiwan.
Translational Medicine Laboratory, Rheumatology Research Center, China Medical University Hospital, Taichung 404, Taiwan.
Int J Mol Sci. 2023 Jun 26;24(13):10645. doi: 10.3390/ijms241310645.
Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.
类风湿关节炎（RA）是一种慢性炎症性疾病，会给动脉粥样硬化性心血管疾病（ASCVD）带来沉重负担。高密度脂蛋白（HDL）颗粒组成不均一，具有多种动脉保护特性，其中一些甚至可能增加 ASCVD 风险。在这项前瞻性和横断面研究中，我们旨在研究 RA 患者的 HDL 大小/代谢物与炎症之间的关系。采用基于 H-NMR 的脂质/代谢组学方法，在 RA 患者和健康对照（HC）受试者之间以及在 RA 患者中有无抗瓜氨酸化肽抗体（ACPA）之间，确定了差异 HDL 相关代谢物。评估 RA 患者中具有鉴别能力的 HDL 相关代谢物与 C 反应蛋白（CRP）之间的相关性。RA 患者的大/超大 HDL 颗粒数、脂质、胆固醇、胆固醇酯、游离胆固醇和磷脂水平更高。与 ACPA 阴性患者相比，ACPA 阳性患者的 L-HDL-C 和 L-HDL-CE 更高，但小/中 HDL-TG 水平更低。CRP 水平与小 HDL 呈负相关。Janus 激酶抑制剂治疗与血清小 HDL 相关代谢物水平升高和 CRP 水平降低有关。我们首次揭示了 RA 炎症与 HDL 大小/代谢物之间的显著关联。在 RA 患者中还观察到 ACPA 阳性与血清 HDL 相关代谢物水平变化之间的潜在联系。
