Abstract

Abstract Systemic juvenile idiopathic arthritis (SJIA) is a chronic autoinflammatory condition of childhood, characterized by remitting fever, transient rash, and relapsing arthritis. The association of macrophage activation syndrome with SJIA and clinical evidence implicating monocyte-derived cytokines IL-1 and IL-6 suggest a key role for monocyte in SJIA pathogenesis. We have previously found monocyte expansion during disease activity (flare), and a normal distribution of the monocyte subsets CD14hiCD16- and CD14loCD16+. We also observed elevated expression of monocyte surface markers CD14 and CD16 in the respective CD14hiCD16- and CD14loCD16+ monocyte subpopulations during disease flare and inactivity (quiescence), suggesting phenotypic alteration of monocytes in SJIA, independent of clinical status. We further analyzed phenotypic and functional alterations of SJIA monocytes in relation to disease activity and in comparison to age- and ethnicity-matched controls, specifically regarding development towards a M1- or M2- polarized phenotype. Gene expression profile, flow-cytometry based analysis of surface markers, baseline and LPS-induced production of cytokines and phosphorylation patterns in response to cytokine stimulation indicate that SJIA monocytes have a mixed M1/M2 phenotype during disease flare. Disease quiescence is associated not with normalization, but with an M2 phenotype, suggesting the existence of a state of compensated inflammation that is broke during disease flare.