No drugs are yet approved for the treatment of primary Sjögren syndrome, despite a large number of clinical trials. Non-conventional approaches can help to identify novel therapeutic targets. Using a drug-repositioning transcriptomic approach, interferon has emerged once again as a major target for intervention in this disease process.
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References
Bodewes, I. L. A., Björk, A., Versnel, M. A. & Wahren-Herlenius, M. Innate immunity and interferons in the pathogenesis of Sjögren’s syndrome. Rheumatology (Oxford) 60, 2561–2573 (2019).
Ivashkiv, L. B. & Donlin, L. T. Regulation of type I interferon responses. Nat. Rev. Immunol. 14, 36–49 (2014).
Felten, R. et al. Identification of new candidate drugs for primary Sjögren’s syndrome using a drug repurposing transcriptomic approach. Rheumatology (Oxford) https://doi.org/10.1093/rheumatology/kead096 (2023).
Verstappen, G. M., Pringle, S., Bootsma, H. & Kroese, F. G. M. Epithelial–immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis. Nat. Rev. Rheumatol. 17, 333–348 (2021).
Juarez, M. et al. A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren’s syndrome. Rheumatology (Oxford) 60, 1364–1375 (2021).
Yang, L. et al. Histone deacetylase 3 contributes to the antiviral innate immunity of macrophages by interacting with FOXK1 to regulate STAT1/2 transcription. Cell Rep. 38, 110302 (2022).
Nusinzon, I. & Horvath, C. M. Positive and negative regulation of the innate antiviral response and beta interferon gene expression by deacetylation. Mol. Cell. Biol. 26, 3106–3113 (2006).
Joshi, S., Kaur, S., Kroczynska, B. & Platanias, L. C. Mechanisms of mRNA translation of interferon stimulated genes. Cytokine 52, 123–127 (2010).
Verstappen, G. M. et al. The transcriptome of paired major and minor salivary gland tissue in patients with primary Sjögren’s syndrome. Front. Immunol. 12, 681941 (2021).
Price, E. et al. Safety and efficacy of filgotinib, lanraplenib and tirabrutinib in Sjögren’s syndrome: a randomized, phase 2, double-blind, placebo-controlled study. Rheumatology (Oxford) 61, 4797–4808 (2022).
Acknowledgements
This publication is part of project number 09150162010166 of the Veni research programme, which is financed by the Dutch Research Council (NWO). The authors are supported by a Dutch Arthritis Society (ReumaNL) Long Term Project Grant (LLP-29).
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The authors are co-applicants on an unrestricted grant by AstraZeneca for NCT05383677 (ANISE-II trial). G.M.V. received consultancy fees from Argenx. F.G.M.K. received consultancy fees from ArgenX and Bristol-Myers Squibb.
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Verstappen, G.M., Kroese, F.G.M. A leading role for interferon as a treatment target in Sjögren syndrome. Nat Rev Rheumatol 19, 468–469 (2023). https://doi.org/10.1038/s41584-023-00991-9
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DOI: https://doi.org/10.1038/s41584-023-00991-9
