Influence of cytokine auto antibodies on serum IFNα activity in SLE (P6287)

Abstract The type-I interferon (IFN-I) family consists of 12 IFN-α subtypes as well as IFN-β and IFN-ω. IFN-α subtypes are thought to play a pivotal role in the pathogenesis of autoimmune diseases such as lupus by enhancing the production of anti-nuclear autoantibodies and driving end organ damage in patients with lupus nephritis. Despite the putative role of IFN-αs in disease, serum IFN-α activity levels are often low or undetectable in lupus patients. Auto antibodies (AAbs) against a single IFNα subtype (IFNα4) have been detected in lupus patients suggesting they may alter serum IFNα activity and disease severity. To better understand this relationship, we have measured total IFNα and IFNα subtype-specific AAbs levels in lupus patient serum. Our results thus far reveal an excellent correlation between IFNα activity and AAb levels, suggesting AAbs may provide an indirect marker of cytokine activity in some patients. Toward this end, we have determined the AAb profile for eleven cytokines implicated in lupus to understand their relationship to IFNα levels and overall disease severity. The resulting cytokine profile will be presented towards the goal of determining the best targets for anti- cytokine therapy in lupus.