Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL) as a Mediator of the Association Between Particulate Matter Exposure and Disease Activity in Systemic Lupus Erythematosus

초록

Background/Purpose: Neutrophil gelatinase-associated lipocalin (NGAL) is an acute-phase glycoprotein increased by inflammatory stimuli, oxidative stress, and tissue injury. Although NGAL is associated with global and renal disease activity in systemic lupus erythematosus (SLE), it is not known whether particulate matter (PM) affects NGAL levels and lupus activity in these patients. Thus, we investigated the mediating role of NGAL in the association between PM10 and PM2.5 exposure and lupus activity in a prospective, longitudinal cohort. Methods: The study enrolled 386 patients from three metropolitan regions in Korea. The daily average PM10 and PM2.5 concentrations were measured using portable air quality monitors and based on data from the National Ambient Air Monitoring System. Urinary NGAL (uNGAL) was measured at the time of enrollment and at 12 months, and disease activity was evaluated using the SLE Disease Activity Index 2000 (SLEDAI-2K) every 3 months for 1 year. Mixed Cox proportional hazard regression was performed to evaluate the associations of PM10 and PM2.5 with uNGAL and SLE disease activity. Results: Changes in PM10 and PM2.5 were associated with changes in uNGAL (β = 1.038, 95% confidence interval [CI]: 1.017–1.059, p < 0.001; β = 1.030, 95% CI: 1.001–1.045, p = 0.013, respectively), and with changes of SLEDAI-2K scores of > 8 over 1 year in SLE patients (β = 0.097, 95% CI: 0.048–0.146, p < 0.001; β = 0.100, 95% CI: 0.054–0.146, p < 0.001, respectively). In addition, changes in uNGAL were significantly associated with changes in SLEDAI-2K scores of > 8 (β = 1.000, 95% CI: 1.000–1.002, p = 0.043). Conclusion: The association between PM exposure and SLE disease activity may be partially explained by uNGAL levels.