INCREASED SERUM LEVEL OF IL-36 RECEPTOR ANTAGONIST IS ASSOCIATED WITH ACTIVE DISEASE IN PATIENTS WITH ADULT-ONSET STILL'S DISEASE

Abstract

Background Adult onset Still’s disease (AOSD) is an inflammatory disorder which was associated with varying level of pro-inflammatory cytokines. However, the role of natural anti-inflammatory molecules has not been evaluated to date. Interleukin (IL) 1 cytokine family is closely related to clinical presentations, disease activity and thus is a target for treatment of AOSD. IL-36 receptor antagonist (Ra) is an anti-inflammatory molecule, but its clinical significance has not been studied in AOSD patients.

Objectives To figure out the role of IL-36Ra in monitoring disease activity in patients with AOSD.

Methods The number of 49 AOSD patients meeting Yamaguchi criteria were recruited. Each patient was serially monitored following clinical course of flare and remission, which presented at least 2 points of change in modified Pouchot’s score. They were divided into two groups by clinical courses, which were predominant systemic symptoms or arthritis. We compared erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin as disease activity markers between flare and remission. Serum levels of inflammatory cytokines, IL-18, IL-37, and IL-36Ra were measured by enzyme-linked immunosorbent assay (ELISA) in each clinical state of AOSD patients.

Results Forty-nine patients with AOSD were included in this study; 40 were women (81.6%) and 9 were men (18.3%), with mean age of 49.08±14.17 years old. The mean duration of follow-up was 6.44±3.87 years, and mean difference of modified Pouchot’s score was 5.37±1.98 between remission and flare. The number of 33 (67.4%) patients had presented systemic symptoms predominantly, while 16 (32.7%) presented arthritis more frequently in their clinical course. In flare state of AOSD, overall inflammatory markers were elevated, including cytokines of IL-18 and IL-37. The serum level of IL-36Ra was 164.04±169.03 pg/mL in active state, compared to 125.36±452.0 in inactive state of AOSD patients (p<0.001). IL-36Ra presented positive correlation with modified Pouchot’s score and inflammatory markers, including CRP (r=0.286, p<0.01), ferritin (r=0.225, p<0.05) and IL-37 (r=0.353, p<0.01), but was not with level of IL-18 and ESR in active AOSD. Distribution of IL-36Ra level was analysed by each clinical course, however, there was no significant difference in level of IL-36Ra by clinical presentations stratified with predominance of arthritis.