Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus

Abstract

Assessments of disease activity and organ damage in systemic lupus erythematosus (SLE) remain challenging because of the lack of reliable biomarkers and disease heterogeneity. Ongoing inflammation can be difficult to distinguish from permanent organ damage caused by previous flare-ups or medication side effects. Circulating soluble urokinase plasminogen activator receptor (suPAR) has emerged as a potential marker of inflammation and disease severity, and an outcome predictor in several disparate conditions. This study was done to evaluate suPAR as a marker of disease activity and organ damage in SLE. Sera from 100 healthy donors and 198 patients with SLE fulfilling the 1982 American College of Rheumatology classification criteria and/or the Fries criteria were analyzed for suPAR by enzyme immunoassay. Eighteen patients with varying degree of disease activity were monitored longitudinally. Disease activity was assessed by the SLE disease activity index 2000 and the physician's global assessment. Organ damage was evaluated by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Compared with healthy control subjects, serum suPAR levels were elevated significantly in patients with SLE. No association was recorded regarding suPAR levels and SLE disease activity in cross-sectional or consecutive samples. However, a strong association was observed between suPAR and SDI (P < 0.0005). Considering distinct SDI domains, renal, neuropsychiatric, ocular, skin, and peripheral vascular damage had a significant effect on suPAR levels. This study is the first to demonstrate an association between serum suPAR and irreversible organ damage in SLE. Further studies are warranted to evaluate suPAR and other biomarkers as predictors of evolving organ damage.

Keywords: 1982 American College of Rheumatology classification criteria; ACR-82; ANA; C-reactive protein; CRP; D(I); D(II); D(III); ELISA; ESR; Fas; HEp-2; IL; Ig; PGA; SDI; SLE; SLE disease activity 2000; SLEDAI-2K; Systemic Lupus International Collaborating Clinics/ACR damage index; TNF; antinuclear antibody; apoptosis stimulating fragment; domain I; domain II; domain III; double-stranded DNA; dsDNA; enzyme-linked immunosorbent assay; erythrocyte sedimentation rate; human epithelial cell line type-2; immunoglobulin; interleukin; physician's global assessment; sFas; soluble Fas; soluble urokinase plasminogen activator receptor; suPAR; systemic lupus erythematosus; tumor necrosis factor; uPAR; urokinase plasminogen activator receptor.