Abstract
Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis.
Highlights
Be associated with the excretion of overproduced proteins, including pro-inflammatory cytokines and chemokines, from chronic inflammatory cells[9]
Analysis of cytokine mRNA and protein in synovial tissues has revealed that a variety of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α,interleukin (IL)-1, and IL-6, as well as chemokines including CCL2 and IL-8 are upregulated in the peripheral blood and the joints of Rheumatoid arthritis (RA) patients[10]
After adjustment for urine creatinine, urinary levels of the three cytokines (IL-6, CCL2, and IL-8) (n = 173) were significantly higher in RA patients than in non-RA control subjects (n = 62) (Fig. 1A,C), which concurs with our previous report demonstrating that RA patients have inflammatory urine[9]
Summary
Be associated with the excretion of overproduced proteins, including pro-inflammatory cytokines and chemokines, from chronic inflammatory cells[9]. We postulate that the urine of RA patients reflects systemic inflammatory status and urinary cytokine and chemokine levels, including IL-6, IL-8, and CCL2, could be potential biomarkers of disease activity and prognosis of RA. To address this issue, we prospectively investigated the relationship between urinary IL-6, IL-8, and CCL2 levels at initial presentation and radiographic progression of RA, which was monitored over three years
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