Adult-onset STING-associated vasculopathy
Year: 2026
Type: article
Study design: Observational Study
Abstract: Genetic contributions to systemic autoimmunity are often considered more significant in children than in adults. As such, genetic evaluation may be more frequently pursued in pediatric rheumatology patients. Motivated by the discovery of a STING-associated vasculopathy with onset in infancy (SAVI) mutation in a patient with adult-onset relapsing polychondritis and systemic lupus erythematosus, we hypothesized that STING gain-of-function mutations might underlie a broader spectrum of autoimmune disease in adults. We systematically screened 43,731 exomes from the Penn Medicine Biobank, revealing five additional unrelated adults with SAVI-associated STING gain-of-function mutations, including several patients with clinical features of SAVI, as well as asymptomatic individuals with type I IFN signatures. We propose the term adult-onset STING-associated vasculopathy (AO-SAVI) to describe these patients. Our findings challenge the conventional symptom-driven diagnostic paradigm, revealing that parallel molecular classification can uncover shared mechanisms and genetic etiologies across seemingly distinct diseases.
Source: Journal of Human Immunity
Authors: Thomas R. Riley, Jonathan J. Kotzin, Debby J. Park, Shubhasree Banerjee, Asako Takanohashi, Adeline Vanderver, Penn Medicine Biobank, Daniel J. Rader, Marylyn D. Ritchie, JoEllen Weaver, Nawar Naseer, Giorgio Sirugo, Afiya Poindexter, Yi-An Ko, Kyle P. Nerz, Meghan Livingstone, Fred Vadivieso, Stephanie DerOhannessian, Teo Tran, Julia Stephanowski, Salma Santos, Ned Haubein, Joseph Dunn, Anurag Verma, Colleen Morse Kripke, Marjorie Risman, Renae Judy, Colin Wollack, Shefali S. Verma, Scott Damrauer, Yuki Bradford, Scott Dudek, Theodore Drivas, Joshua F. Baker, Amanda V. Finck, Jonathan J. Miner
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: U.S. Department of Veterans Affairs, Eli Lilly and Company, Sanofi, University of Pennsylvania, Regeneron Pharmaceuticals, University of Pennsylvania Health System, National Institutes of Health, Perelman School of Medicine, University of Pennsylvania, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences
Awards: G1043879701, G1507378265, G1852790566, G2288164393, G2349321998, G4235927528, G471519714, G4735861120, G4739483508, G6104092673, G7994221527, G853874183, G9000000688, G9000043450, G9000113588, G9000127251, G9000135050, G9000138654, G9000266210, G9000327959, RANKL regulation of human B cell responses, Training Program/Rheumatic Diseases, Mechanisms of STING-associated autoinflammation
OpenAlex ID: W7160877071