Targeting interferons and their pathways in systemic lupus erythematosus |
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Authors: | François Chasset Laurent Arnaud |
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Institution: | 1. AP-HP, Service de Dermatologie et d''Allergologie, Hôpital Tenon, F-75020, Paris, France;2. Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes et Systémiques Rares, Université de Strasbourg, INSERM UMR-S 1109, F-67000 Strasbourg, France |
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Abstract: | Significant advances in the understanding of the molecular basis of innate immunity have led to the identification of interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of Systemic Lupus Erythematosus. Therefore, targeting of IFNs and of their downstream pathways has emerged as important developments for novel drug research in SLE. Based on this, several specific interferon blocking strategies using anti-IFN-α antibodies, anti-type I interferon receptor antibodies, Interferon-α-kinoid, or anti-IFN-γ antibodies have all been assessed in recent clinical trials. Alternative strategies targeting the plasmacytoid dendritic cells (pDCs), Toll-Like Receptors (TLRs)-7/9 or their downstream pathways such as the myeloid differentiation primary-response protein 88 (MYD88), spleen tyrosine kinase (Syk), Janus-kinases (JAKs), interleukin-1 receptor-associated kinase 4 (IRAK4), or the Tyrosine Kinase 2 (TYK2) are also investigated actively in SLE, at more preliminary clinical development stages, except for JAK inhibitors which have reached phase 2 studies. In a near future, in-depth and personalized functional characterization of IFN pathways may provide further guidance for the selection of the most relevant therapeutic strategy in SLE, tailored at the patient-level. |
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Keywords: | Systemic lupus Interferons Interferon-alpha Treatments Systematic review |
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