Usefulness of serum leucine-rich alpha-2 glycoprotein as a disease activity biomarker in patients with rheumatoid arthritis

Abstract

Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-α and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8 ± 14.4 vs. 22.2 ± 6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (γ=0.671; γ=0.612; and γ=0.601, P<0.001, respectively), but not with serum TNF-α levels. Serum LRG levels in patients with an active disease status (DAS28≥2.6) were significantly higher than those in remission (DAS28<2.6) (36.45 ± 14.36 vs. 24.63 ± 8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-α and it may be a novel biomarker for assessing inflammatory activity in patients with RA.

Keywords: Arthritis, Rheumatoid; Disease Activity; Leucine-Rich Alpha-2-Glycoprotein; Tumor Necrosis Factor-alpha.

Fig. 1

Serum leucine-rich alpha-2 glycoprotein (LRG) levels in rheumatoid arthritis (RA) patients and controls. Mean LRG concentrations were significantly elevated in the serum of patients with RA compared with those in healthy controls (P < 0.001).

Fig. 2

Receiver-operating characteristic (ROC) analysis for leucine-rich alpha-2 glycoprotein (LRG) to discriminate between rheumatoid arthritis (RA) and healthy control. It resulted in an area under curve (AUC) of 0.712 (95% CI, 0.619-0.804) and an optimal cut-point at 27 ng/mL. With that cut-off level, the sensitivity was 53.6% and the specificity was 85.4%.

Fig. 3

Differences in serum concentrations of leucine-rich alpha-2 glycoprotein (LRG) between patients with active and inactive rheumatoid arthritis (RA) and healthy controls. Serum concentrations of LRG in the active RA group are higher than those in the inactive RA group and controls (P < 0.001). Patients with inactive RA show higher LRG levels than the controls (P = 0.044).

Fig. 4

Correlations between disease activity parameters and serum concentrations of leucine-rich alpha-2 glycoprotein (LRG) in patients with rheumatoid arthritis (RA). Serum levels of LRG are positively correlated with disease activity score 28 (DAS28) (γ = 0.671, P < 0.001), (A) erythrocyte sedimentation rate (ESR) (γ = 0.612, P < 0.001), (B) C-reactive protein (CRP) (γ = 0.601, P < 0.001), (C) number of tender joints (γ = 0.554, P < 0.001), (D) and number of swollen joints (γ = 0.514, P < 0.001), (E).