A novel STING1-activating mutation is identified in a patient with childhood-onset systemic lupus erythematosus

Abstract

Gain-of-function variants in stimulator of interferon genes (STING1) are known to cause STING-associated vasculopathy with onset in infancy (SAVI), a disorder characterized by cutaneous vasculopathy, interstitial lung disease (ILD), and systemic inflammation. Here, we report a novel STING1 N188H variant in a patient who met the classification criteria for systemic lupus erythematosus (SLE) but lacked typical SAVI features. In vitro assays demonstrated that the N188H variant drives constitutive STING activation and enhances type I interferon signaling. Consistent with this, the patient exhibited elevated interferon-stimulated genes (ISGs) expression, and RNA sequencing confirmed significant upregulation of type I IFN signaling compared to healthy controls. Our findings expand the molecular spectrum of STING-associated disease.