SAT0538 Serum Interleukin-18 and S100A8/A9 as Prediction Markers for Disease Activity in Patients with Inactive Adult-Onset Still's Disease
Authors: J.J. Kim, S.M. Kang, S.W. Lee, S. Lee, I.W. Sohn, D.H. Yoo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Adult-onset Still9s disease (AOSD) is a rare systemic inflammatory disease. Although the pathogenesis of AOSD is still unknown, many proinflammatory cytokines including interleukin (IL)-1, IL-6, IL-18 and TNF-α contribute to many clinical manifestations and laboratory abnormalities. Diagnosis of AOSD and prediction of disease activity are difficult because there are lack of disease specific clinical findings and serologic markers. <h3>Objectives</h3> The aim of this study was to investigate the significance of serum interleukin (IL)-18 and S100A8/A9 protein in the assessment of disease activity among AOSD patients. <h3>Methods</h3> Forty patients satisfying Yamaguchi9s criteria for AOSD, 26 healthy controls and 23 patients with rheumatoid arthritis (RA) were enrolled. We collected clinical data including demographic findings and laboratory findings in active state and inactive state. Serum levels of IL-18 and S100A8/A9 proteins were measured by enzyme-linked immunosorbent assay (ELISA) in each states of AOSD. Activity state was divided by modified Pouchot9s (mPouchot9s) score. Inactive state was defined mPouchot9s score less than 4 at least consecutive 2 months, after 6.2±1.4 months of active state. <h3>Results</h3> There were significantly higher levels of serum IL-18 (107951.1±94440.9 pg/mL) in active state than inactive state of AOSD (14772.2±22126.7 pg/mL), RA patients (333.8±309.0 pg/mL) and healthy controls (350.7±160.4 pg/mL). Although, serum S100A8/A9 protein were significantly higher in active state of AOSD (33340.3±22029.3 ng/mL) than inactive state (11826.5±15368.4 ng/mL), healthy controls (1812.7±2506.1 ng/mL) and RA (13577.5±12893.6 ng/mL), S100A8/A9 in inactive state was not showed different compared to RA patients. The levels of serum IL-18 and S100A8/A9 protein showed mild to moderate correlations with other serologic markers such as WBC, ESR, CRP and ferritin. And they also showed moderate correlations with mPouchot9s score. The cutoff points of differentiating activity in AOSD were determined by receiver operator characteristic (ROC) curve. When using a 24399.85 pg/mL of IL-18 as an AOSD activity marker, sensitivity was 82.5% and specificity was 82.5%. And using a 12101.55 ng/mL of S100A8/A9 protein level showed lower sensitivity (72.5%) and specificity (72.5%) than IL-18. The 25% of AOSD patients with clinically inactive state became active state and/or elevated ESR and CRP within 2 months. AOSD patients showing higher IL-18 and S100A8/A9 protein than activity cutoff points in inactive state, showed disease flare within 2 months [OR=14.0 (2.1-93.2), OR=9.8 (1.9-50.6), respectively]. <h3>Conclusions</h3> Serum IL-18 and S100A8/A9 protein were significantly increased in active AOSD patients compared with inactive AOSD, RA and healthy controls. However, IL-18 was more useful cytokine to distinguish from RA in inactive AOSD compared to S100A8/A9 protein. Serum level of IL-18 and S100A8/A9 protein may be useful predictors of disease activity within several months in inactive state of disease. <h3>Disclosure of Interest</h3> None declared