THU0380 Interleukin-18 (IL-18) as A Biomarker for Diagnosis and Evaluation of Disease Activity in Patients with Adult Onset Still's Disease (AOSD)
Authors: H. Kudela, S. Drynda, J. Kekow
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Establishing the diagnosis of Adult onset Still9s disease is very challenging. Mostly it is still a diagnosis of exclusion. Along with IL-1, IL-6 and TNFα, IL-18 is one of the cytokines which seem to play a pivotal role in the pathogenesis of AOSD. It has been described as potential biomarker to support the diagnosis of AOSD. Regarding the importance of IL-18 as a marker for disease activity published data are so far conflicting. <h3>Objectives</h3> The aim of the study was to contribute to the understanding of the role of IL-18 as a diagnostic marker and its importance as a measure for disease activity in AOSD. <h3>Methods</h3> 30 patients (9 male, 21 female, mean age 41.7, range 19-74) diagnosed with AOSD in our Hospital from June 2007 - May 2013, were included in the study. 18 patients met Yamaguchi criteria, 2 would have met Yamaguchi criteria but had also positive anti-nuclear antibodies. For the remaining we adopted the diagnosis from the records. 20 patients were seen repeatedly. Medical records and laboratory analytes such as CRP, ESR, WBC were collected. IL-18 serum levels were determined using an IL-18 ELISA (MBL, Japan) according to the manufacturer9s instructions. Additionally to the standard serum dilution (1:5) some samples were diluted up to 1:200. In two independent control cohorts (12 healthy controls, 10 RA patients) IL-18 serum levels were analyzed. Disease activity was evaluated with Rau9s criteria and CRP values. Active disease was defined as a Rau9s score ≥2 and/or CrP≥2 ULN. <h3>Results</h3> 22 out of 30 patients showed an active disease with a mean activity score of 3.5 (range 1-6) and a mean CRP value of 79.3 mg/l (range &lt;5.0-208 mg/l), 8 patients were in remission (mean activity score 0.25 (range 0-1); mean CRP 5.7 mg/l (range &lt;5-7.4), when seen for the first time. The mean IL-18 serum levels for all patients was 5705 pg/ml (range 100–408000 pg/ml). IL-18 levels were significantly increased in patients with active AOSD compared to patients in remission with a median of 17400 pg/ml (range 326-408000) and 373 pg/ml (range 100-1455 pg/ml), respectively. In comparison, the median IL-18 levels in the HC and RA cohort were 298 pg/ml and 312 pg/ml. In 14 patients with active disease at the first visit (Rau9s score 3.6, range 0-6) the reduction of disease activity (Rau9s score 0.3, range 0-2) was accompanied by a significant reduction in IL-18 serum levels from median of 19850 pg/ml (range 326 – 408000 pg/ml) to 462 pg/ml (range 20 – 7560 pg/ml) (paired sample T-test p&lt;0.05), IL-18 levels of AOSD patients in remission remained stable. The levels of IL-18 were positively correlated with CRP levels (Pearson correlation, r=0.591, p&lt;0.01) as well as percentage of neutrophils (r=0.434, p&lt;0.05) and ferritin levels (r=0.550, p&lt;0.01). <h3>Conclusions</h3> We could confirm earlier publications that high serum levels of IL-18 in active AOSD are detectable, with up to 1000fold higher concentrations compared to healthy controls and a patient cohort with a chronic inflammatory disease (RA). The results of our study clearly show an association of IL-18 serum levels with disease activity. Our findings emphasize the importance of IL-18 as diagnostic biomarker as well as an additional marker of disease activity. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4914