Impaired serum cholesterol efflux capacity in rheumatoid arthritis and systemic lupus erythematosus

Area of Science:

• Cardiovascular disease research
• Immunology and rheumatology
• Lipoprotein metabolism and function

Background:

• Autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with significantly increased cardiovascular risk, only partially explained by traditional factors.
• High-density lipoproteins (HDL) play a crucial role in reverse cholesterol transport, promoting cholesterol efflux from cells, a process with known anti-atherogenic properties.
• Beyond cholesterol efflux, HDL also modulates the function of endothelial and immune cells, suggesting broader implications in inflammatory and cardiovascular contexts.

Purpose of the Study:

• To investigate and compare the functionality of high-density lipoproteins (HDL) in promoting cellular cholesterol efflux in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
• To evaluate the specific pathways involved in cholesterol efflux capacity (CEC) and their potential correlation with disease characteristics in RA and SLE.

Main Methods:

• Serum cholesterol efflux capacity (CEC) was assessed using radioisotopic ex-vivo systems in 30 RA patients, 30 SLE patients, and 30 healthy controls.
• Measurements focused on apoB-depleted serum to primarily reflect HDL-mediated activity, with methods designed to discriminate between specific cholesterol efflux pathways.
• ATP-binding cassette (ABC) transporter-mediated efflux pathways, specifically ABCA1 and ABCG1, were analyzed.

Main Results:

• Rheumatoid arthritis patients exhibited impaired ATP-binding cassette G1 (ABCG1)-mediated CEC, which correlated with disease activity.
• Systemic lupus erythematosus patients displayed a more complex pattern, including reduced ABCG1-mediated CEC and impaired ATP-binding cassette A1 (ABCA1)-mediated CEC, independent of disease activity.
• The relationship between specific CEC pathways and serum total HDL levels varied between groups; no correlation was found with autoantibody profiles or current therapies.

Conclusions:

• Cholesterol efflux capacity (CEC) is demonstrably impaired in both RA and SLE patients, indicating a functional deficit in HDL's anti-atherogenic properties.
• Each disease exhibits a distinct pattern of CEC impairment, mediated by specific pathways (ABCG1 in RA, ABCA1 and ABCG1 in SLE), and this impairment is not directly dependent on overall serum HDL levels.
• These findings suggest a novel mechanism contributing to the elevated atherosclerotic risk observed in patients with RA and SLE, highlighting CEC as a potential therapeutic target.