The goal of this application is to measure IFNs (IFNalpha, ß, epsilon, kappa, omega and IFN gamma) binding/signaling at the single cell level in peripheral blood of SLE patients.  This will be accomplished using antibodies (Abs) that recognize IFN-receptor Signaling Complexes (IFNSCAbs), but not IFN-receptors or the IFNs alone.  We hypothesize IFNSCAbs, combined with multi-parameter flow cytometry, will provide a direct measure of IFN binding and IFN signaling on blood cell subsets. By measuring IFN signaling in this manner, we hope to improve the correlation between IFN activity/crosstalk and clinical disease parameters. These studies could allow the use of IFN as a biomarker to assess SLE disease activity, which would have broad impact on patient monitoring and assist in characterizing novel SLE therapies.