Longitudinal Evaluation of Lipoprotein Variables in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy

Abstract

Objectives Systemic lupus erythematosus (SLE) associates with accelerated atherosclerotic cardiovascular disease. SLE patients have adverse lipoprotein parameters, but little is known about how these change with treatment and disease activity. The NMR LipoProfile test® contains a glycoprotein signal termed GlycA, an inflammatory marker, which has not been evaluated in SLE. We assessed patients longitudinally to determine how lipoproteins and GlycA change with active SLE. Methods Sera from selected clinical visits of patients in the Hopkins Lupus Cohort were analyzed for lipoprotein and GlycA levels. Univariate and multivariate analyses were performed to evaluate lipoprotein parameters and their relationship to ethnicity, disease activity, prednisone use and hydroxychloroquine therapy. Results 52 patients were included over 229 visits. Adverse changes in lipoprotein parameters with disease activity were demonstrated. For each point increase in SLEDAI there was a decrease in high-density lipoprotein (HDL) even after adjusting for corticosteroid use. Prednisone associated with higher VLDL, LDL, HDL and triglycerides. Hydroxychloroquine associated with more favorable parameters. GlycA levels were higher than in normal populations and increased with disease activity. Conclusion Adverse changes in lipoprotein profiles associated with SLE activity and prednisone therapy. This gives insight into mechanisms of atherosclerosis in SLE. Favorable lipoprotein parameters occurred in those taking hydroxychloroquine. GlycA increased with disease activity and was higher than in healthy populations.

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

“…In a separate SLE cohort, mean GlycA levels were somewhat higher in female patients with high disease activity vs. patients with low or no disease activity and nonafflicted women [42,92]. In a longitudinal analysis of SLE activity, GlycA increased significantly along with increases in SLEDAI [92]. Taken together, GlycA may have utility for assessing disease activity in patients with autoimmune diseases such as RA and SLE.…”

“…In the same study, GlycA levels were positively associated with ESR, hsCRP, Eselectin, sICAM-1 and triglycerides, but not with creatinine, SLE Disease Activity Index (SLEDAI), SLE Collaborating Clinics (SLICC/ACR) Damage Index, or coronary calcium scores [91]. In a separate SLE cohort, mean GlycA levels were somewhat higher in female patients with high disease activity vs. patients with low or no disease activity and nonafflicted women [42,92]. In a longitudinal analysis of SLE activity, GlycA increased significantly along with increases in SLEDAI [92].…”

“…GlycA was shown to be higher in RA and systemic lupus erythematosus (SLE) [47,91,92]. In a cross-sectional study that included 166 RA patients and 90 control subjects, GlycA concentrations were higher in RA patients compared to control subjects [47].…”

Update on cardiovascular disease in lupus

“…(95) Hydroxychloroquine has been shown to inhibit IFN production by pDCS, which may account for the reduced risk. (96) In murine models of SLE, hydroxychloroquine decreased reactive oxygen species production via NADPH, improving nitric oxide availability and preventing endothelial dysfunction.…”

Why targeted therapies are necessary for systemic lupus erythematosus

“…Hydroxychloroquine is thought to work in part by increasing lysosomal pH in antigen presenting cells, reducing toll-like receptor signaling resulting in decreased activation of dendritic cells and through the reduction of interferon production(40), amongst other mechanisms(41). In additional to disease specific benefits in SLE, hydroxychloroquine has been shown to have lipid lower properties(42, 43), anti-thrombotic effects(41) and hypoglycemic actions(44). Hydroxychloroquine is a safe, non-immunosuppressive therapy with good tolerability.…”