Systemic lupus erythematosus: from an adverse event of interferon administration to a disease with new treatment options
Keywords:
Systemic lupus erythematosus, interferon, etiology, pathogenesis, autoimmune, autoantibodies, immune complex, plasmacytoid dendritic cells, natural interferon producing cells, treatment, anifrolumab
Abstract
Patients with systemic lupus erythematosus (SLE) display an increased expression of type I interferon (IFN)-regulated genes, a so-called IFN signature. This discovery was preceded by the observation in Uppsala that patients with malignant diseases treated with type I IFN occasionally developed autoimmune diseases, including SLE. The adverse event of IFN treatment was the start of an intensive search for the role of the type I IFN system in patients with spontaneously occurring SLE. A key finding by our group was the detection in patients with SLE of endogenous IFN-inducers that could activate plasmacytoid dendritic cells (pDC) to IFN production. Further studies revealed the mechanisms by which these cells are triggered to a continuous IFN synthesis. We could also identify a large number of risk genes for SLE and several molecules connected to type I IFN production and response. My group early on suggested the possibility that some of these molecules are suitable therapeutic targets in SLE, but also other IFN-driven diseases. Antibodies against the type I IFN receptor (anifrolumab) have recently shown efficacy in clinical trials for SLE, and anifrolumab is now approved as a treatment for this disease. Several other drugs targeting critical molecules in the IFN signaling pathways – including BCDA-2 (Blood Dendritic Cell Antigen 2), TLR7/8 (Toll-like receptor 7/8), and TYK2 (Tyrosine Kinase 2) – are currently in early clinical phases, potentially expanding therapeutic options for SLE. In this review, several important observations regarding the role of the type I IFN system in SLE and therapeutic implications are discussed.
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References
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Published
2025-12-17
How to Cite
Rönnblom , L. (2025). Systemic lupus erythematosus: from an adverse event of interferon administration to a disease with new treatment options. Upsala Journal of Medical Sciences, 130, e13677. https://doi.org/10.48101/ujms.v130.13677
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