Deborah Lenschow, MD, PhD
Washington University, St. Louis, MO
Exploring the role of interferon kappa in SLE pathogenesis
The Study and What It Means to Patients
"Several treatments that target a group of blood factors known as interferons are in development for lupus. We are examining an unusual interferon — interferon kappa — to find out whether it has harmful or beneficial effects and should targeted in therapies."
Interferons are blood proteins produced by our immune system that help fight viruses and other infections. In small amounts they are of great benefit but in lupus they are massively overproduced, causing widespread activation of the immune system and inflammation. Treatments targeting interferons are in clinical trials for lupus. However 17 different factors make up the interferons, and we do not know which are critical in disease. We are studying one specific interferon — interferon-kappa — which appears to behave differently than other interferons and has not been looked at in the context of lupus before. Our results will tell us whether it is important for interferon targeted therapies to block interferon-kappa.
Systemic lupus erythematosis is a chronic autoimmune disease characterized by the loss of tolerance to nuclear antigens and the development of pathogenic autoantibodies, resulting in injury to multiple organ systems. Studies of patients with SLE and work in murine models of lupus have strongly implicated type I IFNs in its pathogenesis. Type I IFNs are composed of up to 13 IFN-alphas and a single IFN-beta, -kappa, -epsilon, and -omega. All of these subtypes bind to the type I IFN receptor to mediate their actions, but little is known about their individual biological properties. IFN-kappa is constitutively produced by keratinocytes and also produced by DCs and macrophages. We have recently begun characterizing mice in which the IFN-kappa gene has been deleted. Surprisingly, mice lacking IFN-kappa are protected from viral infection, suggesting that its function is distinct from the other subtypes of IFN. We propose that IFN-kappa binding to the type I IFN receptor results in distinct activation of the receptor as compared to other subtypes of IFN, which may have important implications for its activity in SLE. Studies outlined in this proposal will compare the activities of IFN-kappa and IFN-a and evaluate the function of IFN-kappa during SLE pathogenesis.
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