Studies involving larger cohorts with long-term follow-up are needed to further support the clinical efficacy of this drug. Newer biologicals like rilonacept (IL1 Trap) and canakinumab (anti-IL1β monoclonal antibody) are also now being studied in management of SoJIA.[1, 3, 4] IL-6 also plays a key role in SoJIA. The best defined association is with the G variant of a promoter polymorphism of the IL-6 genes.[13] Yokota et al. demonstrated the efficacy of tocilizumab, a genetically engineered humanized recombinant

anti-IL-6 receptor antibody, in SoJIA[14] and later confirmed this by a randomized controlled HSP activation trial.[15] IL-18 has also been linked to SoJIA. A study by De Jager et al.[16] demonstrated that the mechanism of the impaired natural killer (NK) cell function in SoJIA involved a defect in IL-18R phosphorylation. Thus, based on the pattern of cytokine expression

profile and the exquisite response to specific therapy tailored for the same, SoJIA is believed to be biologically distinct from the other subtypes of JIA. Unlike the oligoarticular and polyarticular subtypes of JIA, no distinctive HLA associations have been reported in SoJIA. Genetic polymorphisms also appear to influence the outcome in SoJIA, as exemplified by the work done by Benedetti et al.[17] who showed that a polymorphism selleck chemicals in the macrophage migration inhibitory factor gene (i.e. MIF 173*C allele) was a poor prognostic marker in SoJIA. Ogilvie et al.[18] compared a small cohort of active SoJIA and inactive SoJIA and reported significant differences

in gene expression profiles in peripheral blood mononuclear cells, thereby showing that gene expression profiles may differ not only between various subtypes of JIA but also within a given subtype depending on the magnitude of disease activity. During the last decade, there has been lot of speculation on the putative role of Forkhead Box Protein 3 (FOXP3) expressing T regulatory cells (Tregs) in pathogenesis of autoimmune diseases. Wehrens et al.[19] studied Treg function Phospholipase D1 in JIA and observed that Tregs from peripheral blood as well as the inflamed joints were fully functional but they failed to control autoimmune inflammation due to resistance in effector cells because of PKB/c-akt hyperactivation in effector cells. Stelmaszczyk-Emmel et al.[20] demonstrated in a small cohort of oligoarticular and polyarticular JIA that percentage of Tregs in JIA patients was significantly decreased in comparison with healthy controls. However, the clinical implications of these studies are not clear. Understanding the genetic mechanisms, cytokine profiles and cytokine polymorphisms in different subtypes of JIA has directly impacted the formulation of clinical management protocols of JIA. These changes are reflected in the 2011, and subsequently the 2013, American College of Rheumatology (ACR) recommendations.