THU0381 High levels of circulating type i, ii and iii interferons define distinct patient subsets with active systemic lupus erythematosus (SLE). (12th June 2018)

• Record Type: Journal Article
• Authors: Oke, V.; Gunnarsson, I.; Dorschner, J.M.; Zickert, A.; Niewold, T.B.; Svenungsson, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 406
• Page End: 406
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.4783
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Interferons (IFN) play a major role in SLE pathogenesis. 1 IFNs type I (predominately IFN-αs) are of major importance, 2 but IFN type II (IFN-γ) and IFNs type III (λ) have also important roles. 3, 4 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. References: [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. Acknowledgements: 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. Disclosure of Interest: None declared