Abnormal HDL quality and capacity to acquire phospholipids in patients with rheumatoid arthritis: effect of tofacitinib and tocilizumab

Abstract

Background: Patients with rheumatoid arthritis (RA) have high risk of cardiovascular disease, which may be due to dysfunctional HDL. The anti-inflammatory agents tofacitinib (janus kinase inhibitor) and tocilizumab (antibody against interleukin 6 receptor) have shown therapeutic efficacy. The aim of our work was to evaluate lipids, HDL characteristics and HDL capacity to acquire phospholipids (PL) from lipolysis of triglyceride-rich lipoproteins (TGRL), and the effect of tofacitinib and tocilizumab in RA patients. Sixteen RA female patients and 4 controls were recruited from the Rheumatology Service, BA Italian Hospital. Eight patients were treated with tofacitinib and 8 with tocilizumab. HDL subfractions were isolated by density gradient ultracentrifugation and their components were measured with commercial kits. HDL fractions were incubated with TGRL, lipoprotein lipase, and the fluorescent TopF to evaluate HDL capacity to acquire PL. Results were analyzed employing the statistical package SPSS 17.0. Plasma triglycerides (TG) were higher in RA patients than in controls, with non-significant lower HDL-C. HDL was enriched in TG and total proteins, and depleted in free and esterified cholesterol (FC and EC). In turn, TG content was higher and EC lower in HDL2b, HDL2a and HDL3a. HDL capacity to acquire PL was reduced in patients as compared with controls [56 (51-59) vs. 102 (63-104) %, respectively; p<0.05]. Moreover, treatment with tofacitinib or tocilizumab produced no considerable changes in lipids or lipoprotein composition. However, HDL capacity to bind released PL increased at 3 and furthermore at 6 months after treatment with tofacitinib, and at 6 months with tocilizumab. Conclusion: RA patients displayed HDL with abnormal subfraction distribution and chemical composition, which probably conditioned the deficiency to acquire PL from lipolysis of TGRL. This altered antiatherogenic function of HDL was reversed by treatment with both tofacitinib and tocilizumab.