Background Establishing the diagnosis of Adult onset Still's 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.
Objectives 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.
Methods 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 manufacturer's 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 Rau's criteria and CRP values. Active disease was defined as a Rau's score ≥2 and/or CrP≥2 ULN.
Results 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 <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 <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 (Rau's score 3.6, range 0-6) the reduction of disease activity (Rau's 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<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<0.01) as well as percentage of neutrophils (r=0.434, p<0.05) and ferritin levels (r=0.550, p<0.01).
Conclusions 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.
Disclosure of Interest : None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.