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SP0174 The value of type i interferon signature to stratify patients
  1. L. Rönnblom
  1. Uppsala University, Uppsala, Sweden


Since the first reports 2003 of an increased expression of type I interferon (IFN) regulated genes in cells from patients with SLE, a number of studies have demonstrated that many systemic inflammatory autoimmune diseases display this overexpression of type I IFN regulated genes, now known as an IFN signature. This is true for a majority of patients with SLE, but also large proportion of patients with primary Sjögrens syndrome, myositis, systemic sclerosis and rheumatoid arthritis (RA). The so called type I interferonopathies is a group of rare Mendelian diseases with a very strong IFN signature. Other autoimmune diseases, such as type I diabetes, also display an IFN signature. Type I IFN seems to be most important for inducing the IFN signature, but it’s clear that type II and type III IFNs can contribute to the IFN signature. Besides the expression of type I IFN regulated genes, recent studies have shown that patients with SLE and other autoimmune disease, have epigenetic changes in IFN regulated gene, which are hypomethylated. Thus, there are strong evidences that type I IFN system activation is a key event in many autoimmune diseases. Can the IFN signature help us to stratify patients in order to predict risk for major organ manifestations, disease outcome or response to treatment? Early studies showed that patients with active disease and more severe disease manifestations usually have a more prominent IFN signature, which still is true. However, recent studies have revealed that the IFN signature needs to be combined with a broader analysis of expressed genes. For instance, a plasmablast signature seems to correlate best with SLE disease activity and a neutrophil signature associates with lupus nephritis. For treatment stratification, it’s perhaps not surprising that SLE patients with a high IFN signature have a better treatment response to type I IFN inhibition, compared to IFN low patients. At least when type I IFN receptor inhibition has been used to downregulated the type I IFN response. In RA, the IFN signature at baseline predict a poor response to TNF-alpha treatment as well as nonresponse to B-cell depleting therapy. In conclusion, there are several indications that the type I IFN signature is a valuable biomarker for patient stratification. However, we are just at the brink of the understanding how to apply this signature in clinical practice.

Disclosure of Interest L. Rönnblom Grant/research support from: AstraZeneca, Consultant for: UCB, AstraZeneca, Speakers bureau: Biogen

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