Increased serum levels of β₂-GPI-Lp(a) complexes and their association with premature atherosclerosis in patients with rheumatoid arthritis

Abstract

Background: Our recent study found the existence of complexes of β₂-glycoprotein I (β₂-GPI) with lipoprotein(a)[Lp(a)] in circulation and the complex concentrations were increased in sera of systemic lupus erythematosus patients. The concentration of β₂-GPI-Lp(a) and its relationship with premature atherosclerosis were evaluated in rheumatoid arthritis (RA) patients.

Methods: Serum concentrations of β₂-GPI-Lp(a) were measured in 53 active RA patients and 40 healthy controls by a "sandwich" ELISA. β₂-GPI-ox-LDL, ox-Lp(a), ox-LDL and anti-β₂-GPI were also measured by ELISAs. In addition, inflammatory markers were examined.

Results: Serum β₂-GPI-Lp(a) (1.12±0.25 U/ml vs. 0.87±0.19 U/ml, P<0.0001) and β₂-GPI-ox-LDL (1.01±0.20 U/ml vs. 0.80±0.08 U/ml, P<0.0001) concentrations in RA were both significantly higher than those of controls. Ox-Lp(a) (8.38±6.69 mg/l vs. 5.49±4.31 mg/l, P<0.05) and ox-LDL (0.68±0.65 mg/l vs. 0.37±0.13 mg/l, P=0.001) were also higher in RA than in controls. The area under the ROC curve (AUC) for β₂-GPI-Lp(a) (0.787) was larger than for ox-Lp(a) (0.731). AUC of β₂-GPI-ox-LDL (0.858) was also larger than for ox-LDL (0.785). β₂-GPI-Lp(a) and β₂-GPI-ox-LDL were positively correlated with ox-Lp(a), ox-LDL and CRP, respectively.

Conclusions: β₂-GPI-Lp(a) complex concentrations increased in active RA. Inflammation and oxidative stress in RA contribute to the increase of ox-Lp(a) and subsequently the formation of β₂-GPI-Lp(a).