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

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  1 , Susanne Drynda  1 , Anke Lux  2 , Gerd Horneff  3   4 , Joern Kekow  1
Affiliations

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 et al. BMC Rheumatol. .

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).

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Conflict of interest statement

The study has been performed in accordance with the Declaration of Helsinki and was approved by the ethics committee (Ethik-Kommission der Medizinischen Fakultät der Otto-von-Guericke-Universität, Leipziger Straße 44, 39,120 Magdeburg) of the Medical Faculty of the Otto-von-Guericke-University Magdeburg under the reference number 71/99. All participants provided written informed consent. For the participating children written informed consent was obtained from their parents/legal guardians.Not applicable.The authors declare that there is no conflict of interest regarding the publication of this article. The study centers did not receive any financial support nor was there a conflict of interest regarding data analysis or manuscript writing. The clinical part of the study, the statistics and manuscript preparation were performed within the scope of the duties of the hospitals involved without additional funding. The authors did not receive any funding, grants, honoraria or any other form of recognition or compensation of any kind from a sponsor.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Box-and-whisker plot of IL-18 serum levels in adult cohort
Fig. 2
Fig. 2
Box-and-whisker plot of CRP serum levels in adult cohort
Fig. 3
Fig. 3
Box-and-whisker plots for IL-18 serum levels in children’s cohort
Fig. 4
Fig. 4
Box-and-whisker plots for serum CRP in children’s cohort
See this image and copyright information in PMC

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