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We have begun examining serum levels of Type I and III interferons in normal and autoimmune donors by ELISA and a Type I reporter gene activity assay to determine if there are expression pattern signatures of these diseases. Samples were obtained from normal donors and patients with Systemic Lupus Erythematosus, Rheumatoid Arthritis or Multiple Sclerosis and assayed for IFN-α), IFN-β, IFN-ω, and IFN. Normal controls had little detectable IFN-α, IFN-ω, or Type I IFN activity. Low levels of IFN-β were detected in 15% of the normal controls. Approximately 35% of the normal controls had detectable IFN-λ. In the Lupus samples, 45% had detectable IFN-α. IFN-ω and IFN-β were detected in 20 and 40%, respectively, of the Lupus samples. Overall, greater than 80% of the Lupus samples had detectable Type-I IFN. Rheumatoid arthritis samples may have elevated IFN-β and IFN-ω relative to normal controls, but not IFN-α. Multiples sclerosis samples had a slight tendency towards elevated IFN-β. A low percentage of Lupus and multiple sclerosis samples had detectable Type-I IFN activity by the reporter gene assay. None of the samples displayed significant differences in Type III IFN expression. Multiplex ELISA was used to examine a subset of the samples for cytokine profiles and in Lupus samples IL-13 was decreased. In arthritis samples IL-8 and IL-23 were elevated, while in Multiple Sclerosis samples IL-2, IL-4 and IL-10 were elevated. The implications of these results will be discussed.