THU0381 High levels of circulating type i, ii and iii interferons define distinct patient subsets with active systemic lupus erythematosus (SLE)
Authors: V. Oke, I. Gunnarsson, J.M. Dorschner, A. Zickert, T.B. Niewold, E. Svenungsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Interferons (IFN) play a major role in SLE pathogenesis.<sup><sup>1</sup></sup> IFNs type I (predominately IFN-αs) are of major importance,<sup><sup>2</sup></sup> but IFN type II (IFN-γ) and IFNs type III (λ) have also important roles.<sup><sup>3,4</sup></sup> How the levels of circulating IFNs type I, type II and type III relate to each other, and if they associate with any particular SLE disease manifestations is not known. <h3>Objectives</h3> We investigated serum levels of type I, type II, and type III IFNs and explored how these measurements relate to each other and to specific organ manifestations in patients with SLE. <h3>Methods</h3> We studied 497 well-characterised SLE patients and 322 controls. Functional type I IFN-activity (IFN-activity) was measured by WISH cell assay. IFN-α and IFN-λ1 were measured by ELISA, and IFN-γ by MSD 30-plex assay. High IFN-activity/levels were defined as value over 3rd quartile of the measurement. <h3>Results</h3> SLE patients had higher levels of all investigated IFNs. IFN-activity correlated with IFN-α and IFN-γ. High functional IFN-activity associated with active SLE in most domains: weight loss, fatigue, fever, rash, lymphadenopathy, arthritis and nephritis. The IFN-γ high group had active disease with higher rates of nephritis, arthritis, leuko-, lymphopenia and Sm, SmRNP, RNP68, Ro52 and Ro60 autoantibodies. A higher proportion of the IFN-α high group had active rash, lymphadenopathy, Ro52 and La autoantibodies, while rates of antiphospholipid antibodies/syndrome, vascular events and renal affection were lower. High IFN-λ1 associated with anti-nucleosome autoantibodies and lymphopenia. <h3>Conclusions</h3> High type I IFN functional activity is associated with active SLE in the majority domains. A severe SLE phenotype, including active nephritis, arthritis and anti-Sm/SmRNP autoantibodies is associated with high IFN-γ, while rash and a benign cardiovascular profile are linked to high serum IFN-α. Isolated increase in IFN-λ1 is only coupled to lymphopenia and antinucleosome antibodies. Our findings demonstrate that several IFNs can be elevated at the same time in SLE and the importance of IFN-γ has so far been underscored. Sub-setting of SLE patients might be important when planning future clinical trials. <h3>References</h3> [1] Niewold TB, Hua J, Lehman TJA, et al. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun2007;8:492–502. doi:10.1038/sj.gene.6364408 [2] Bengtsson AA, Sturfelt G, Truedsson L, et al. Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus2000;9:664–71. [3] Oke V, Brauner S, Larsson A, et al. IFN-λ1 with Th17 axis cytokines and IFN-α define different subsets in systemic lupus erythematosus (SLE). Arthritis Res Ther2017;19:139. doi:10.1186/s13075-017-1344-7 [4] Machold KP, Smolen JS. Interferon-gamma induced exacerbation of systemic lupus erythematosus. J Rheumatol1990;17:831–2. <h3>Acknowledgements</h3> We are grateful to Susanna Eketjäll, Eva Jemseby, Johanna Gustafsson, Marie Wahren-Herlenius, Susanna Brauner, Ola Börjesson, Marika Kvarnström, Susanne Pettersson, Sonia Möller, Jill Gustafsson for help with different parts of the project. <h3>Disclosure of Interest</h3> None declared