Janus Kinase Inhibition and SLE: Is this a Plausible Treatment Option for SLE?
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Other CTD: Inflammatory Myopathies and Sjogren’s (P Basharat and JFL Albayda, Section Editors)
Janus Kinase Inhibition and SLE: Is this a Plausible Treatment Option for SLE? Ayida Al Khalili, MD, FRCPC1 Jan P. Dutz, MD, FRCPC2,* Address 1 Dermatology Unit, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman *,2 Department of Dermatology and Skin Science, University of British Columbia, 835 West Tenth Avenue, Vancouver, BC, V5Z 4E8, Canada Email: [email protected]
* Springer Nature Switzerland AG 2020
This article is part of the Topical Collection on Other CTD: Inflammatory Myopathies and Sjogren's Keywords Jakinib I JAK inhibition I JAK/STAT pathway I Systemic lupus erythematosus I Cutaneous lupus erythematosus I Chilblain lupus I Tofacitinib I Baricitinib I Ruxolitinib I Upadacitinib I Filgotinib
Abstract Purpose of review Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease. There is a need for newer therapies to achieve disease control and reduce steroid related morbidity and mortality. Janus Kinase (JAK) inhibitors (Jakinibs) represent a new class of oral therapeutic, which targets cytokine receptor signaling thus blocking cytokineinduced gene transcription. In this review, we assess the current evidence of efficacy of Jakinibs for the various clinical forms of SLE. Recent findings The key role of interferon signaling in SLE is well documented. JAK inhibition can normalize abnormal expression of interferon-related genes in SLE. Murine models have been used to demonstrate the efficacy of Jakinibs in preventing and ameliorating features or SLE including nephritis, skin inflammation, vascular dysfunction, and serological markers. Case reports and small series suggest that Jakinibs may be used to treat SLE and cutaneous lupus erythematosus (CLE). A recent clinical trial suggests that baricitinb may have therapeutic utility in SLE. Summary Jakinibs may have particular efficacy for the management of CLE and cutaneous forms of monogenic lupus (chilblain lupus). Ongoing studies will clarify the utility of Jakinibs for the treatment of various manifestations of SLE.
Other CTD: Inflammatory Myopathies and Sjogren’s (P Basharat and JFL Albayda, Section Editors)
Introduction Janus kinases (JAK) are intracellular tyrosine kinases that act as essential signaling hubs for cytokine receptors [1]. Their name is derived from Janus, the two-faced Roman god of doors and new beginnings as these molecules were noted to have two kinase domains [2]. The JAKs interact with STAT (signal transducers and activators of transcription) molecules modulating the cellular effects of cytokines. Consequently, the JAK/STAT pathway is a critical signaling cascade that links cytokines, chemokines, and growth factors to the transcription of STAT dependent genes. Activation of JAKs results in STAT phosphorylation and nuclear translocation leading to transcription of dependent genes [3]. The importance of JAK signaling for the regulation of the immune system (both adaptive and innate immunity) and hematopoiesis has been
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