Th e fi eld of autoimmunity has proven a fertile ground for blood transcriptional studies. Alterations in transcript abundance in the blood of patients refl ect the sustained response against self-antigens and, more generally, uncon trolled infl ammatory processes. Such diseases often present with recurring-remitting patterns of activity, with episodes of fl aring that may be refl ected by fl uctuations in transcript abundance. Th e work has initially focused on diseases with clear systemic involvement such as systemic lupus erythematosus (SLE) [20, 21] . Multiple cell types and soluble mediators, including IL10 [22, 23] and IFNγ [24] [25] [26] , have been proposed to be at the center of lupus pathogenesis. While some scattered evidence indicated the potential role of type I interferon in lupus, several observations did not support the hypothesis: fi rst, not every SLE patient has detectable serum type I IFN levels [27] ; second, dysregulation of type-I IFN production is not found in most murine SLE-models [28] ; and third, genetic linkage and association studies had not identifi ed candidate lupus susceptibility genes within the IFN pathway [29] . However, in one of our earliest microarray studies we demonstrated that all but one of the pediatric patients exhibited upregulation of IFNinducible genes, and the only patient lacking this signature had been in remission for over 2 years [20] . In addition, it was found that treating SLE patients with high dose IV steroids, which are used to control disease fl ares, results in the silencing of the IFN signature. A surprise from these initial studies was the absence of type I IFN gene transcripts in the face of an abundance of IFN-inducible ones in the blood cells of SLE patients. A likely explanation is that the cells producing type I IFN, and therefore transcribing these genes, migrate to sites of injury. Altogether, results from microarray studies played a key role in convincing the community of the potential importance of type I IFN in SLE pathogenesis [15, [30] [31] [32] [33] [34] . A phase Ia trial to evaluate the safety, pharmacokinetics, and immunogenicity of anti-IFNα monoclonal antibody (mAb) therapy in adult SLE patients was recently conducted [35] . Th e antibody elicited a specifi c and dosedependent inhibition of overexpression of type I IFNinducible genes in both whole blood and skin lesions from SLE patients, at both the transcript and protein levels. As expected, overexpression of BLyS/BAFF, a type I IFN-inducible gene, also decreased with treatment. Th us, this fi rst trial supports the proposed central role of type I IFN in human SLE.