Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations

Innate immunity to viral infection involves induction of the type I IFN response; however, dysfunctional regulation of this pathway leads to inappropriate inflammation. Here, we evaluated a nonconsanguineous family of mixed European descent, with 4 members affected by systemic inflammatory and autoimmune conditions, including lupus, with variable clinical expression. We identified a germline dominant gain-of-function mutation in TMEM173, which encodes stimulator of type I IFN gene (STING), in the affected individuals. STING is a key signaling molecule in cytosolic DNA-sensing pathways, and STING activation normally requires dimerization, which is induced by 2'3' cyclic GMP-AMP (cGAMP) produced by the cGAMP…

• AN
  Agence Nationale de la Recherche

  Awards: ANR-14-CE14-0026, CE14-0026-01, ANR-14-CE14-0026-01, 249816, 10-IAHU-01, ANR-10-IAHU-01, ANR-10
• IN
  Institut National de la Santé et de la Recherche Médicale

  Awards: ANR-10-IAHU-01, 249816