THU0512 WHAT IS HIDDEN BEHIND SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS, ADULT ONSET STILL’S DISEASE AND SECONDARY MACROPHAGIC ACTIVATION SYNDROME. THE UTILITY OF THE BIOMARKERS

Abstract

Background: Systemic Juvenile Idiopathic Arthritis (SJIA) and adult onset Still’s disease are rare diseases of unknown etiology that share several clinical and laboratory features. The pathogenesis of these two diseases is complex and multifactorial, with an important role of innate immunity: activation of neutrophils and macrophages and increased levels of cytokines dependent on the activation of the inflammosome. A proportion of these patients will develop a Macrophage activation syndrome (MAS), a serious and life-threatening complication. Objectives: To identify immunological markers that allow a differential diagnosis between patients with inactive SJIA, active SJIA or MAS. To evaluate if there are differences between biomarkers in SJIA and adult onset Still’s disease Methods: Observational, prospective and multicenter study. Inclusion criteria: patients with SJIA or adult onset Still’s disease, followed in Paediatric or Adult Rheumatology Department from 5 Madrid hospitals. Group 1: Patients with active SJIA or adult onset Still’s disease +/- diagnosis of secondary MAS at the first visit, have been followed-up performing a second clinical and analytical visit at 3 months. Group 2: Patients with inactive SJIA or adult onset Still’s. Clinical and analytical data were collected, PBMCs were obtained before and after treatment, and several leukocyte subtypes were evaluated by flow cytometry (FACS). The intracytoplasmic expression of TNF-α, IL-1b and IL-6 in monocytes was determined by flow cytometry before and after stimulation with lipopolysaccharides (LPS) in the presence of monensin (Golgi inhibitor). In addition, IL-18 levels were determined by ELISA in all visits. Results: A total of 25 patients were included (18 SJIA and 7 adult onset Still’s diseases), 2 of them being excluded from the analysis because exclusions criteria. 30,4% patients presented MAS at the first visit (5 SJIA and 2 adult onset Still’s disease) and other 2 at some time during the disease. The median of IL-18 was 296.1 (CI 108.3-346.0) in patients who have never had MAS and 899.85 (CI: 397.32-1095.6) in the other group. Patients with active MAS had a CD4/CD8 ratio close to the lower limit (1.1 +/- 0.1 SD) reflecting a decrease in the CD4 + population and an increase in CD8 +. On the other hand, the rest of the groups presented a CD4/CD8 ratio of 2.6 +/- 0.5 SD in patients without disease activity and 2.0 +/- 0.7 SD in patients with active SJIA or adult onset Still’s disease but without MAS. No significant differences were found between patients with SJIA or adult onset Still’s disease. Conclusion: The results of this study show that the analysis of three determinations:%CD4,%CD8 and the CD4/CD8 ratio can help in the early detection of patients with MAS secondary to SJIA or adult onset Still’s disease. The determination of IL-18 has been in our study a marker of MAS, similar to several published studies. No significant differences were found in the immunological tests between patients with SJIA and adult onset Still’s disease with active or inactive disease. Reference: [1] Weiss ES et all Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome. Blood. 2018 Mar 29;131(13):1442-1455 Disclosure of Interests: None declared