Comparative study of Interleukin-18 (IL-18) serum levels in adult onset Still's disease (AOSD) and systemic onset juvenile idiopathic arthritis (sJIA) and its use as a biomarker for diagnosis and evaluation of disease activity

Holger Kudela; Susanne Drynda; Anke Lux; Gerd Horneff; Joern Kekow

doi:10.1186/s41927-019-0053-z

Comparative study of Interleukin-18 (IL-18) serum levels in adult onset Still's disease (AOSD) and systemic onset juvenile idiopathic arthritis (sJIA) and its use as a biomarker for diagnosis and evaluation of disease activity

BMC Rheumatol. 2019 Feb 28:3:4. doi: 10.1186/s41927-019-0053-z. eCollection 2019.

Authors

Holger Kudela¹, Susanne Drynda¹, Anke Lux², Gerd Horneff^{3

4}, Joern Kekow¹

Affiliations

¹ 1Clinic of Rheumatology, University of Magdeburg, Sophie-von-Boetticher-Strasse 1, 39245 Vogelsang-Gommern, Germany.
² 2Institute for Biometry and Medical Informatics, University of Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
³ Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Arnold-Janssen Strasse 29, 53757 Sankt Augustin, Germany.
⁴ 4Department of Pediatric and Adolescents medicine, Medical Faculty, University Hospital of Cologne, Cologne, Germany.

Abstract

Background: Signs and symptoms establish the diagnosis of adult onset Still's disease (AOSD) as well as of systemic onset juvenile idiopathic arthritis (sJIA). The published data regarding the importance of IL-18 as a marker for diagnosis and disease activity so far are conflicting. The aim of this study was to clarify the role of IL-18 as a diagnostic and disease activity marker in AOSD and sJIA.

Methods: Thirty adult patients diagnosed with AOSD and twenty children diagnosed with sJIA were included in the study. Clinical and laboratory data were obtained retrospectively for each patient visit whenever IL-18 serum levels were determined. IL-18 levels were determined by ELISA. Sixty-five adults and twenty-three children presenting with fever and/or arthritis who did not meet the criteria for a diagnosis of AOSD or sJIA served as comparison groups. Rau's criteria and CRP values were used to evaluate disease activity.

Results: IL-18 levels were significantly elevated in patients with active AOSD compared to AOSD patients in remission and to the comparison group with a median of 16,327 pg/ml, 470 pg/ml, and 368 pg/ml, respectively (p < 0.001). Analogous to AOSD in active sJIA, the median IL-18 serum level was significantly higher with 21,512 pg/ml than in the comparison group with 2580 pg/ml (p < 0.001).At our cut-off point of 5000 pg/ml, the calculated specificity of IL-18 to establish the diagnosis of AOSD was 96.9%, and the sensitivity 63.3% (AUC = 0.870, p < 0.001). For the diagnosis of sJIA, a cut-off value of 10,000 pg/ml was chosen with a specificity of 100% and a sensitivity of 60% (AUC = 0.774, p = 0.003). At a cut-off value of 5000 pg/ml, the specificity was 62% and the sensitivity 65%.

Conclusions: This study gives further evidence to earlier publications of elevated IL-18 serum levels in active AOSD and sJIA, with up to 1000-fold higher concentrations compared to other rheumatic diseases. A clear association of IL-18 serum levels with disease activity in AOSD was found. The results support the use of IL-18 as an important biomarker in AOSD and sJIA.

Keywords: Adult onset Still’s disease (AOSD); Disease activity; Interleukin-18 (IL-18); Systemic onset juvenile arthritis (sJIA).