Spreafico et al. (22) utilized a 12 color flow panel to allow for the sensitive detection of a circulating subset of pathogenic CD4+ T cells that are phenotypically similar to CD4+ T cells from the synovial micro-environment of JIA patients (22).These circulating pathogenic lymphocytes (CPLs) correlate significantly with disease activity and are increased in patients resistant to methotrexate and anti-TNFα therapy. Here, TNF is linked to juvenile idiopathic arthritis.