Interfering with Interferons: targeting the JAK-STAT pathway in complications of systemic juvenile idiopathic arthritis (SJIA).

Abstract

Systemic juvenile idiopathic arthritis (SJIA) is distinguished from other forms of JIA by the prevalence of severe, life-threatening complications macrophage activation syndrome (SJIA-MAS) and lung disease (SJIA-LD). Alternative therapeutics are urgently needed, as disease pathogenesis diverges from what is observed in SJIA, and currently available biologics are insufficient. SJIA-MAS, defined by a cytokine storm and dysregulated proliferation of T-lymphocytes, and SJIA-LD which presents with lymphocytic interstitial inflammation and pulmonary alveolar proteinosis, are both thought to be driven by interferons, in particular type II interferon (IFN-y). Involvement of IFNs and a possible crosstalk of type I IFNs with existing biologics indicate a distinct role for the JAK-STAT signaling pathway in the pathogenesis of SJIA-MAS and SJIA-LD. Here, we review this role of JAK-STATs and interferons in SJIA complications and discuss how new insights of ongoing research are shaping future therapeutic advances in the form of JAK inhibitors and antibodies targeting IFNs.