The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients

• Published in: International journal of molecular sciences Vol. 24; no. 13; p. 10645
• Main Authors: Chang, Ching-Kun, Chiang, En-Pei Isabel, Chang, Kuang-Hsi, Tang, Kuo-Tung, Chen, Po-Ku, Yip, Hei-Tung, Chen, Chu-Huang, Chen, Der-Yuan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.06.2023; MDPI
• Subjects: Arthritis; Arthritis, Rheumatoid - metabolism; Biological products; Blood lipids; Body mass index; C-reactive protein; Cholesterol; Cholesterol, HDL; Correlation analysis; Cross-Sectional Studies; Disease; Humans; Inflammation; Inflammation - complications; Kinases; Lipids; Lipoproteins, HDL; Membrane lipids; Metabolites; Prospective Studies; Proteins; Rheumatoid arthritis; Rheumatoid factor; Tofacitinib; Taiwan; rheumatoid arthritis (RA); anti-citrullinated peptide antibodies (ACPA); lipid metabolites; inflammation; high-density lipoprotein (HDL)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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 1H-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.