Background/Purpose: Establishing the diagnosis of adult onset Still’s disease (AOSD) as well as of systemic onset juvenile idiopathic arthritis (sJIA) is very challenging. Mostly it is still a diagnosis of exclusion. Along with IL-1β, IL-6 and TNFα, IL-18 is one of the cytokines which seem to play a pivotal role in the pathogenesis of both diseases. It has been described as a potential biomarker to support the diagnosis of AOSD and sJIA. Regarding the importance of IL-18 as a marker for disease activity published data are so far conflicting. The aim of the study was to clarify the role of IL-18 as a diagnostic marker and its importance as a measure for disease activity in AOSD and sJIA.

Methods: Thirty adult patients diagnosed with AOSD and twenty children diagnosed with sJIA were included in the study.  Twenty adults and three children were analyzed repeatedly.  At each visit patients underwent clinical evaluation and laboratory analysis. IL-18 serum levels were determined using an IL-18 ELISA (MBL, Japan) according to the manufacturer’s instructions. As comparison groups served 65 adults and 23 children with other rheumatic diseases. To evaluate the disease activity Rau’s criteria and CRP values were used.  Active disease was defined as a Rau’s score ≥2 and/or CRP≥ 2 ULN. 

Results: In 83 samples from 30 AOSD patients IL-18 levels were determined. At the time of blood sample collection clinical parameters were obtained as well. In active disease (n=27) patients showed a mean activity score of 3.9±1.4 and a mean CRP value of 106.5±86.1 mg/l. Patients in remission (n=43) showed a mean activity score of 0.14±0.35, and mean CRP value of 5.6±1.5 mg/l. IL-18 levels were significantly increased in patients with active AOSD compared to patients in remission and to the comparison group with a median of 16327 pg/ml, 470 pg/ml, and 368 pg/ml, respectively (p<0,001). In active disease (n=16) the sJIA cohort showed a mean activity score of 3.4±1.0 and mean CRP value of 133.9±81.8 mg/l.  Analogous to AOSD in active sJIA the median IL-18 serum level with 21512 pg/ml was significantly higher than in the comparison group (n=25) with a median IL-18 serum level of 2580 pg/ml (p<0.001) and a mean CRP value of 67.6±77.7 mg/l .

For evaluation of IL-18 serum levels as marker for AOSD or sJIA a receiver operating characteristic curve analysis was used.  At a cutoff point of 5000 pg/ml IL-18 specificity for AOSD was 96.9 %, and sensitivity 63.3 % (AUC=0.870, p<0.001). For diagnosis of sJIA in children a cutoff value of 10000 pg/ml was chosen with a specificity of 100 % and a sensitivity of 60 % (AUC=0.774, p = 0.003).

In 11 AOSD patients with active disease at the first visit (Rau’s score 4.2±1.5) the reduction of disease activity (Rau’s score 0.4±0.7) went along with a significant reduction in IL-18 serum levels from medians of 12500 pg/ml to 402 pg/ml (Wilcoxon sign rank test p<0,001).  

Conclusion: We could confirm earlier publications that highly elevated IL-18 serum levels are common in active AOSD and sJIA, with up to 1000fold higher concentrations compared to other rheumatic diseases. A clear association of IL-18 serum levels with disease activity in AOSD was found. The results give further evidence for the use of IL-18 as diagnostic biomarker in AOSD and sJIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-18-il-18-as-a-biomarker-for-diagnosis-and-evaluation-of-disease-activity-in-patients-with-adult-onset-stills-disease-and-systemic-onset-juvenile-idiopathic-arthritis/