AB0001 INTERFERON SIGNATURE IN CHILDREN WITH CHRONIC NON-BACTERIAL OSTEOMYELITIS AND IT’S DYNAMIC AFTER BISPHOSPHONATES TREATMENT

Abstract

Background:Chronic non-bacterial osteomyelitis (CNO) is an immune-mediated chronic inflammatory bone disease which predominantly affects children and adolescents. The pathogenesis of CNO related to imbalance between pro-inflammatory and anti-inflammatory cytokines. Interferon-I mediated pathway is associated with pathogenesis of different pediatric rheumatic diseases, such as juvenile systemic lupus erythematosus (jSLE), juvenile dermatomyositis (JDM), systemic onset of juvenile idiopathic arthritis (soJIA), and, most of all, with macrophage activation syndrome. The data on interferon-I- regulated pathway in CNO is absent. NSAIDs, non-biologic and biologic anti-inflammatory drugs and bisphosphonates (BF) are treatment options for patients with CNO. The main adverse event of BF is a flu-like syndrome probably caused by the excessive cytokine release stimulated by BF.Objectives:The aim of our study was to evaluate activity of Interferon-I mediated pathway in CNO patients and it’s dynamics after BF treatment.Methods:This prospective study included children with CNO requiring BF treatment (n=9), patients with soJIA (n=8), JDM (n=11) and jSLE (n=40) and healthy controls (HC, n=21). The activity of Interferon-I mediated pathway was assessed using interferon I score (IFN1 score). The score represented the median expression of 5 IFN1-regulated genes (IFI44L, IFI44, IFIT3, LY6E, MX1) measured by quantitative real-time PCR. Patients with CNO were treated with standard 3-day regimen (1 mg/kg/day). We measured interferon score before pamidronate (Day 0, n=9) and after (Day 3, n=7).Results:Median interferon score was 1.09 (0.96; 1.67) in CNO patients, 1.95 (1.3; 5.75) in soJIA, 7.6 (1.78; 29.0) in JDM and 16.9 (2.55; 40.3) in jSLE and 0.95 (0.82; 1.17) in HC (p=0.00001). Where were no difference in the IFN1 score between CNO and HC (p=0.222). In 6/7 CNO patients interferon score increased after pamidronate (p=0.015). The median interferon score after pamidronate increased and became 3.06 (0.87; 4,9, p=0.043); this may possibly explain the development of BF-related flu-like symptoms (cytokine release syndrome).Conclusion:While interferon I-regulated pathway is not directly associated with CNO pathogenesis, BF likely activates interferon-I-regulated pathway and thus could be a possible cause of flu-like syndrome.This work supported by the Russian Foundation for Basic Research (grant № 18-515-57001).Disclosure of Interests:None declared