TNF and juvenile idiopathic arthritis: Notably, disease association within the TRAF1-C5 locus38–40 and epigenetic dysregulation within the TRAF1 locus of CD4 T cells have been detected in patients with JIA.41 Studies using TRAF1−/− mice revealed a TRAF1 negative regulatory role in T-cell response to TCR and TNFα signalling.25TRAF1−/− T cells show enhanced proliferation in response to TCR and TNFα stimulation resulting in NF-κB and AP-1 activation.25