Article Text

THU0031 Role of Polymorphonucleates in the Pathogenesis of Systemic Juvenile Idiopathic Arthritis and Still's Disease: A Proof of Concept Study
  1. F. Magnotti1,
  2. O.M. Lucherini1,
  3. C. De Clemente1,
  4. R. Talarico2,
  5. G. Emmi3,
  6. M. Galeazzi1,
  7. R. Cimaz3,
  8. L. Cantarini1
  1. 1University of Siena, Siena
  2. 2University of Pisa, Pisa
  3. 3University of Florence, Florence, Italy


Background Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are autoinflammatory disorders characterized by neutrophilia and abnormal innate immunity response [1]. It has been hypothesized a pathogenic role of neutrophils, because of patients neutrophilia, maybe related to the typical higher production of pro-inflammatory cytokines, like IL-1β, whose role in these disorders should explain the efficacy of IL-1 blockers [2, 3]. IL-1β is synthesized as inactive form and its activation is mediated by the NLRP3 inflammasome [4]. Increased release of this cytokine in the extracellular environment lead to a positive feedback loop that perpetuates and amplifies itself stimulation [5]. This mechanism as well as neutrophils' activation state could be modified in sJIA and AOSD.

Objectives Our aim was to verify possible differences between sJIA and Still's patients compared to healthy donors, in term of PMNs responsiveness to the extracellular environment and activation state.

Methods PMNs were obtained from heparinised venous blood of sJIA patients (n=6), AOSD patients (n=4) and healthy controls (HC, n=8). All patients' samples were collected during stages of active or non-active disease, according to international disease activity criteria used for the assessment of each disease. After lipopolysaccharide (LPS) treatment, IL-1β content in PMNs supernatants was measured by ELISA assay. CD11b expression levels were measured by flow cytometry, together with intracellular ROS levels through the H2DCFDA ROS-indicator.

Results In comparison with HC, sJIA PMNs showed an increased IL-1β secretion after LPS stimulation (p<0.01). No differences were observed in AOSD patients compared to HC. About neutrophils activation state, higher intracellular ROS levels were detected in PMNs of sJIA patients (p<0.05) than HC at basal condition. Moreover, also CD11b surface marker expression levels, were higher at baseline in sJIA (p<0.01) respect HC. A similar trend was also observed in AOSD patients.

Conclusions Data from our proof of concepts study suggest a possible involvement of PMNs in the pathogenesis of sJIA and AOSD, since they seem more active respect healthy ones and more sensitive to pro-inflammatory stimuli. Although further studies are necessary to confirm and validate this hypothesis, the trend observed may have a potential role in the direction of future therapeutic studies.


  1. Pay, S., et al., A multicenter study of patients with adult-onset Still's disease compared with systemic juvenile idiopathic arthritis. Clin Rheumatol, 2006. 25(5): p. 639-44.

  2. Mellins, E.D., et al., Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol, 2011. 7(7): p. 416-26.

  3. Mavragani, C.P., et al., Adult-Onset Still's Disease: From Pathophysiology to Targeted Therapies. Int J Inflam, 2012. 2012: p. 879020.

  4. Martinon, F., et al., The inflammasomes: guardians of the body. Annu Rev Immunol, 2009. 27: p. 229-65.

  5. Frosch, M., et al., The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1beta form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum, 2009. 60(3): p. 883-91.

Disclosure of Interest None declared

Statistics from

Request permissions

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.