Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients
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Alice Hadchouel
- Fonction : Auteur
- PersonId : 762110
- ORCID : 0000-0001-7451-9890
Laureline Berteloot
- Fonction : Auteur
- PersonId : 786606
- ORCID : 0000-0001-9681-3142
Isabelle Melki
- Fonction : Auteur
- PersonId : 766552
- ORCID : 0000-0002-8057-333X
- IdRef : 158851897
Alexandre Belot
- Fonction : Auteur
- PersonId : 781111
- ORCID : 0000-0003-4902-5332
- IdRef : 115823824
Vincent Bondet
- Fonction : Auteur
- PersonId : 746608
- IdHAL : vincent-bondet
- ORCID : 0000-0002-6534-0984
Darragh Duffy
- Fonction : Auteur
- PersonId : 746816
- IdHAL : darragh-duffy
- ORCID : 0000-0002-8875-2308
- IdRef : 201316919
Mathieu Fusaro
- Fonction : Auteur
- PersonId : 800975
- ORCID : 0000-0002-5332-3626
Gillian Rice
- Fonction : Auteur
- PersonId : 767243
- ORCID : 0000-0002-4223-0571
Jacques Rivière
- Fonction : Auteur
- PersonId : 774331
- ORCID : 0000-0003-1055-2063
Luis Seabra
- Fonction : Auteur
- PersonId : 806099
- ORCID : 0000-0002-4678-3026
Pere Soler-Palacin
- Fonction : Auteur
- PersonId : 797540
- ORCID : 0000-0002-0346-5570
Guillaume Thouvenin
- Fonction : Auteur
- PersonId : 763642
- ORCID : 0000-0003-0528-5458
Stefano Volpi
- Fonction : Auteur
- PersonId : 791249
- ORCID : 0000-0002-7129-868X
Carine Wouters
- Fonction : Auteur
- PersonId : 764842
- ORCID : 0000-0002-6426-8845
Brigitte Bader-Meunier
- Fonction : Auteur
- PersonId : 764839
- ORCID : 0000-0001-8476-8196
- IdRef : 058551522
Yanick Crow
- Fonction : Auteur
- PersonId : 11918
- IdHAL : yanick-crow
- ORCID : 0000-0001-7211-7564
- IdRef : 227205359
Résumé
Background: Gain-of-function mutations in STING1 underlie a type I interferonopathy termed SAVI (STING-associated vasculopathy with onset in infancy). This severe disease is variably characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease (ILD).
Objective: To describe a cohort of patients with SAVI.
Methods: Assessment of clinical, radiological and immunological data from 21 patients (17 families) was carried out.
Results: Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most were symptomatic from infancy, but late onset in adulthood occurred in 1 patient. Systemic inflammation, skin vasculopathy, and ILD were observed in 19, 18, and 21 patients, respectively. Extensive tissue loss occurred in 4 patients. Severity of ILD was highly variable with insidious progression up to end-stage respiratory failure reached at teenage in 6 patients. Lung imaging revealed early fibrotic lesions. Failure to thrive was almost constant, with severe growth failure seen in 4 patients. Seven patients presented polyarthritis, and the phenotype in 1 infant mimicked a combined immunodeficiency. Extended features reminiscent of other interferonopathies were also found, including intracranial calcification, glaucoma and glomerular nephropathy. Increased expression of interferon-stimulated genes and interferon α protein was constant. Autoantibodies were frequently found, in particular rheumatoid factor. Most patients presented with a T-cell defect, with low counts of memory CD8+ cells and impaired T-cell proliferation in response to antigens. Long-term follow-up described in 8 children confirmed the clinical benefit of ruxolitinib in SAVI where the treatment was started early in the disease course, underlying the need for early diagnosis. Tolerance was reasonably good.
Conclusion: The largest worldwide cohort of SAVI patients yet described, illustrates the core features of the disease and extends the clinical and immunological phenotype to include overlap with other monogenic interferonopathies.