IMPAIRED ABCG1-MEDIATED SERUM CHOLESTEROL EFFLUX CAPACITY IN PATIENTS WITH RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS.

Aim: Accelerated atherosclerosis associated with autoimmune diseases is partly due to immune system dysregulation aggravating cardiovascular damage, but little is known on lipid metabolism derangement in this condition. Serum capacity to promote cholesterol efflux from macrophages (CEC) is the first limiting step of the atheroprotective reverse cholesterol transfer process, mainly reflects HDL function and inversely correlates to subclinical atherosclerosis in vivo. We intend verifying whether CEC is altered in rheumatoid arthritis (AR) and systemic lupus erithematosus (SLE) patients. Methods: CEC is measured by a validated ex vivo system using H3-cholesterol in 30 AR and 30 SLE patients, and in 30 age and sex-matched healthy subjects. ABCG1-mediated CEC tests were completed, SR-BI-mediated CEC was determined in AR patients and in control subjects so far, and ABCA1 is under evaluation. Results: ABCG1-mediated CEC in AR and SLE patients is significantly lower than in control subjects (6.045±0.195, 5.74±0.327, 7.13±0.195, respectively, p<0.005 AR vs controls, p<0.0003 SLE vs controls). Correlation between ABCG1-mediated CEC and serum HDL, present in controls (p=0.02), is absent in autoimmune patients. SLE patients as a group showed the lowest ABCG1-mediated CEC in spite of the highest HDL serum level (p=0.0001 vs controls). SR-BI-mediated CEC did not differ between AR and controls. Conclusions: the selective impairment of ABCG1-mediated CEC, independent of HDL serum levels, found in AR and SLE patients is the first demonstration of dysfunction and loss of atheroprotective activity of HDL in these disorders and may represent a tool to better understand accelerated atherosclerosis in autoimmune diseases.