Differential Impairment of Serum Cholesterol Efflux Capacity in Patients with Rheumatoid arthritis and Systemic Lupus Erythematosus

Background: 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. Moreover, the relevance of CEC is strengthened by recent evidence of an impact of cholesterol efflux on inflammatory and immune functions of macrophages and endothelial cells. We measured the four main CEC pathways in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Methods: aqueous diffusion (AD)-, SR-BI-, ABCG1- and ABCA1-mediated CEC was measured by validated radioisotopic ex vivo systems in 30 AR and 30 SLE patients, and in 30 age and sex-matched healthy subjects. Results: SR-BI-mediated CEC (mean±SEM % efflux) was increased in SLE patients (3.84±0.19) as compared to controls (3.20±0.20) and RA patients (2.78±0.17). ABCG1-mediated CEC was reduced in RA and more markedly in SLE (6.04±0.25 and 4.36±0.34, respectively) as compared to controls (7.13±0.2%). ABCA1-mediated CEC was impaired in SLE (2.55±0.16) as compared to controls and RA patients (3.14±0.19 and 3.54±0.30, respectively). AD-mediated CEC did not differ between the three populations studied. ABCG1-mediated CEC inversely correlated with the disease activity score DAS28 in RA patients. SLE patients as a group showed the lowest ABCG1-mediated CEC in spite of the highest HDL serum level. The correlation between ABCG1-mediated CEC and serum HDL, detected in controls and in SLE patients, was absent in RA. The correlation between ABCG1-mediated and SR-BI-mediated CEC detected in controls and RA patients was absent in SLE. Conclusion: we report here for the first time a marked and differential CEC impairment in patients with RA and SLE, independent of HDL serum levels, that not only demonstrates a dysfunction and loss of atheroprotective activity of HDL with respect to cholesterol metabolism, but also points to the existence of specific underlying mechanisms in each disease, possibly beyond inflammation. Moreover, the impairment of ABCG1-mediated cholesterol efflux in autoimmune patients, that correlated with disease activity in the RA group, might also have an impact in inflammatory and immune reaction involving macrophages and endothelial cells.