Adult-onset STING-associated vasculopathy
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.
Authors
- Jonathan J. Miner (ORCID: https://orcid.org/0000-0001-9551-2962)
- Jonathan J. Kotzin (ORCID: https://orcid.org/0000-0001-5179-2034)
- Theodore Drivas
- Anurag Verma (ORCID: https://orcid.org/0000-0002-5063-9107)
- Ned Haubein
- Shubhasree Banerjee (ORCID: https://orcid.org/0000-0003-0903-1949)
- Asako Takanohashi (ORCID: https://orcid.org/0000-0003-3292-1595)
- Giorgio Sirugo (ORCID: https://orcid.org/0000-0002-0244-6343)
- Marjorie Risman
- Amanda V. Finck
- Colleen Morse Kripke (ORCID: https://orcid.org/0009-0007-3117-685X)
- Nawar Naseer (ORCID: https://orcid.org/0000-0002-0700-7155)
- Afiya Poindexter
- Fred Vadivieso
- Julia Stephanowski
- Kyle P. Nerz
- Salma Santos
- Thomas R. Riley (ORCID: https://orcid.org/0009-0003-0194-7562)
- Yuki Bradford
- Meghan Livingstone
- Renae Judy
- Marylyn D. Ritchie
- Adeline Vanderver (ORCID: https://orcid.org/0000-0002-6290-6751)
- Yi-An Ko
- Debby J. Park (ORCID: https://orcid.org/0000-0002-1029-7253)
- Scott Dudek
- Joshua F. Baker (ORCID: https://orcid.org/0000-0003-0799-7563)
- Scott Damrauer
- Teo Tran
- Daniel J. Rader
- Colin Wollack
- Shefali S. Verma
- Stephanie DerOhannessian
- Joseph Dunn
- Penn Medicine Biobank
- JoEllen Weaver
Institutions
- Children's Hospital of Philadelphia (US)
- Parker Institute for Cancer Immunotherapy (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Journal of Human Immunity
- Published
- 2026-04-10
- DOI
- https://doi.org/10.70962/jhi.20250235
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00