THU0513 WHOLE BLOOD CELLS FROM PATIENTS WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS (SJIA) IN CLINICAL INACTIVE DISEASE DISPLAY A DYSREGULATED RESPONSE TO TLR-4 STIMULATION
Authors: Antonia Pascarella, Manuela Pardeo, Ivan Caiello, Claudia Bracaglia, Marianna Rossi, Giulia Marucci, Emanuela Sacco, Fabrizio De Benedetti, Giusi Prencipe
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic juvenile idiopathic arthritis (sJIA) is a polygenic autoinflammatory disease. Innate immune mechanisms appear to play a central role in the pathogenesis of the disease. Nevertheless, a better understanding of the pathophysiology of sJIA is still needed to identify patients responsive to IL-1 or IL-6 targeted therapies. <h3>Objectives:</h3> In this study, we evaluated the production of IL-1β, IL-6 and TNF-α by fresh whole blood cells isolated from sJIA patients in disease remission, after stimulation with the TLR-4 ligand lipopolysaccharide (LPS), and we investigated whether sJIA patients that respond or not-respond to treatment with the IL-1 receptor antagonist anakinra show a different response. <h3>Methods:</h3> We collected fresh whole blood samples from sJIA patients during clinical inactive disease (inactive sJIA, n=19) and sJIA patients during active disease (active sJIA n=4). Active and inactive disease was defined at time of sampling. As controls, fresh whole blood samples from healthy subjects (HS, n=10) were used. Whole blood cells were left unstimulated or stimulated with 10ug/mL of LPS for 24 hours. Cytokine levels (IL-1β, IL-6 and TNF-α) released in the supernatants were measured by ELISA. Response to anakinra was defined as achievement of clinical inactive disease off glucocorticoids at 6 months after initiation of anakinra treatment. <h3>Results:</h3> We found that LPS-stimulated cells from inactive sJIA patients released significantly higher amounts of all the inflammatory cytokines tested, compared to HS (p&lt;0.01). In addition, cells from inactive sJIA patients produced significantly higher levels of IL-1β also compared to active sJIA patients (p&lt;0.05). When we divided inactive sJIA patients in two groups (responders and non-responders), depending on the clinical response to anakinra treatment, we observed that in both groups of patients IL-1β, IL-6 and TNF-α levels were significantly higher than those observed in HS. In addition, we found that LPS-stimulated whole blood cells from non-responder inactive sJIA patients released significantly higher levels of IL-1β and TNF-α compared to responder inactive sJIA patients. <h3>Conclusion:</h3> Our preliminary results show a dysregulated production of inflammatory cytokines by whole blood cells from sJIA patients in remission disease, when stimulated with a TLR-4 agonist. <h3><b>Disclosure of Interests:</b>&nbsp;:</h3> Antonia Pascarella: None declared, Manuela Pardeo: None declared, Ivan Caiello: None declared, Claudia Bracaglia: None declared, Marianna Rossi: None declared, Giulia Marucci: None declared, Emanuela Sacco: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Giusi Prencipe: None declared