OBJECTIVE: Type I interferons (IFNs) play an important role in the pathogenesis 
of systemic lupus erythematosus (SLE). This phase Ia trial was undertaken to 
evaluate the safety, pharmacokinetics, and immunogenicity of anti-IFNalpha 
monoclonal antibody (mAb) therapy in SLE. During the trial, we also examined 
whether overexpression of an IFNalpha/beta-inducible gene signature in whole 
blood could serve as a pharmacodynamic biomarker to evaluate IFNalpha 
neutralization and investigated downstream effects of neutralizing IFNalpha on 
BAFF and other key signaling pathways, i.e., granulocyte-macrophage 
colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), tumor necrosis 
factor alpha (TNFalpha), and IL-1beta, in SLE.
METHODS: Affymetrix Human Genome U133 Plus 2.0 microarrays were used to profile 
whole blood and lesional skin of patients receiving standard therapy for mild to 
moderate SLE. Selected IFNalpha/beta-inducible proteins were analyzed by 
immunohistochemistry.
RESULTS: With the study treatment, we observed anti-IFNalpha mAb-specific and 
dose-dependent inhibition of overexpression of IFNalpha/beta-inducible genes in 
whole blood and skin lesions from SLE patients, at both the transcript and the 
protein levels. In SLE patients with overexpression of messenger RNA for BAFF, 
TNFalpha, IL-10, IL-1beta, GM-CSF, and their respective inducible gene 
signatures in whole blood and/or skin lesions, we observed a general trend 
toward suppression of the expression of these genes and/or gene signatures upon 
treatment with anti-IFNalpha mAb.
CONCLUSION: IFNalpha/beta-inducible gene signatures in whole blood are effective 
pharmacodynamic biomarkers to evaluate anti-IFNalpha mAb therapy in SLE. 
Anti-IFNalpha mAb can neutralize overexpression of IFNalpha/beta-inducible genes 
in whole blood and lesional skin from SLE patients and has profound effects on 
signaling pathways that may be downstream of IFNalpha in SLE.