Tofacitinib relieves symptoms of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy caused by 2 de novo variants in TMEM173.

Authors: Seo, Jieun and Kang, Jung-Ah and Suh, Dong In and Park, Eun-Byeol and Lee, Cho-Rong and Choi, Sun Ah and Kim, Soo Yeon and Kim, Yeji and Park, Sang-Heon and Ye, Michael and Kwon, Soon-Hak and Park, June Dong and Lim, Byung Chan and Lee, Dong Hun and Kang, Suk-Jo and Choi, Murim and Park, Sung-Gyoo and Chae, Jong-Hee

To the Editor: Stimulator of interferon genes (STING), which is encoded by transmembrane protein 173 (TMEM173), is an important mediator in initiating innate immune responses by detecting aberrant DNA species or cyclic di-GMP-AMP (cGAMP) in the cytosol and driving synthesis of type I interferon.1-3cGAMP molecules, which are produced by cyclic GMP-AMP synthase, bind to STING homodimers embedded in the endoplasmic reticulum membrane and eventually cause phosphorylation of interferon regulatory factor 3 by activating Tank-binding kinase 1 (TBK1). Patients with activating mutations of STING display early onset of chronic inflammation and vasculopathy caused by increased type I interferon signaling, a condition termed STING-associated vasculopathy with onset in infancy (SAVI).2,3Improved understanding of STING’s function and its implications in disease pathogenesis has suggested new potential avenues of disease treatment options through modulating STING signaling pathway components.

Journal: The Journal of allergy and clinical immunology
DOI: 10.1016/j.jaci.2016.10.030
Year: 2016

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