WAIKOLOA, HAWAII — Recent developments underscore the critical role the type I interferon system plays in the pathogenesis of systemic lupus erythematosus, according to a dermatology and immunology researcher.
“Type I interferon may be a cornerstone of lupus therapy in the future,” predicted Dr. David Fiorentino of Stanford (Calif.) University.
Type I interferon also appears to be central to the pathogenesis of numerous other autoimmune diseases, he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.
The type I interferon system is emerging as a particularly attractive therapeutic target. There are 13 subtypes of interferon-α, all binding to the same receptor. Several companies are developing biologic agents that down-regulate the type I interferon pathway by blocking interferon-α; preliminary reports are positive, Dr. Fiorentino said.
Interferon-α appears to induce autoimmunity, and it is known that interferon-α levels are increased in the skin, blood, and kidneys of patients with SLE. Interferon levels correlate with disease activity, and interferon-α blockade results in improvement in mouse models of lupus, he said.
The most persuasive evidence that type I interferon plays a key role in lupus has come from recent genetic studies. High serum interferon-α activity has been shown to be a complex heritable trait (Genes Immun. 2007;8:492-502).
Earlier this year, two genome-wide studies resulted in identification of 10 new genetic variants conferring an increased risk of SLE (N. Engl. J. Med. 2008;358:900-9; Nat. Genet. 2008;40:204-10). Some of these genes encode components of the type I interferon pathway associated with activation of the innate immune system, while others are involved in the adaptive immune response.
Dr. Fiorentino commended an editorial by Dr. Mary K. Crow of the Hospital for Special Surgery, New York, which accompanied the gene scan studies and incorporated the findings into an updated model of SLE pathogenesis (N. Engl. J. Med. 2008;358:956-61).
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