Keith, Michael P.

Abstract Processes that lead to clinical illness in SLE years before diagnosis are not well characterized. This study evaluates the temporal relationship between autoantibody production, cytokine levels and the onset of SLE. Serial sera from 60 SLE cases before diagnosis with no ACR criteria to SLE classification (average timespan=4.4 years) and matched healthy controls (HC) were obtained from the DODSR. Sera samples were tested for autoantibodies (BioPlex2200), C-reactive protein (hs-CRP), Von Willebrand’s Factor (VWF) and 32 soluble inflammatory mediators, including cytokines, chemokines, and soluble receptors. Patient samples before ACR classification had significant (p < 0.01) alterations in 16 soluble mediators of inflammation, as well as VWF and hs-CRP. TNF Receptor levels, TNFRI, TNFRII, BLyS, and APRIL, dramatically increased as lupus classification approached (p < 0.001). The increase in TNFR shedding parallels the accumulation of autoantibodies in SLE cases. Interferon (IFN)-associated mediators of inflammation, IFN-γ, IP-10, MIG, and MIP-1α (p < 0.01), were also increased leading up to classification. That these alterations are present prior to the transition to active SLE suggests that multiple perturbations in immune-mediated inflammatory processes occur long before clinical classification and suggest that high-risk, pre-clinical individuals, can be identified before their illness is clinically manifested and damage occurs.