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Article Dans Une Revue Journal of Allergy and Clinical Immunology: In Practice Année : 2021

Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients

1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
2 Service d'immuno-hématologie pédiatrique [CHU Necker]
3 Service de Pneumologie Allergologie [CHU Necker]
4 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
5 Service de radiologie pédiatrique [CHU Necker]
6 AP-HP Hôpital universitaire Robert-Debré [Paris]
7 Urgences pédiatriques [Hôpital de la Timone - APHM]
8 U932 - Immunité et cancer
9 HCL - Hospices Civils de Lyon
10 Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases [CIRI]
11 IP - Institut Pasteur [Paris]
12 Immunologie Translationnelle - Translational Immunology lab
13 Hôpital Princesse Grace [Monaco]
14 Women’s and Children’s Hospital [Adelaide]
15 CHU Notre Dame des Secours [Jbeil]
16 Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM]
17 CCML - Centre Chirurgical Marie Lannelongue
18 Hôpital Necker - Enfants Malades [AP-HP]
19 IRCCS Istituto Giannina Gaslini [Genoa, Italy]
20 IRCCS Ospedale Pediatrico Bambino Gesù = Bambino Gesù Children’s Hospital
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 PCCEI - Pathogenesis and Control of Chronic and Emerging Infections
23 Vall d'Hebron University Hospital [Barcelona]
24 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
25 University Hospitals Leuven [Leuven]
26 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
27 MAHSC - Manchester Academic Health Science Centre
28 VHIR - Vall d’Hebron Research Institute
29 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
30 CHU Trousseau [APHP]
31 Queensland Children's Hospital
32 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
33 Service de pathologie [CHU Necker]
34 CdF (institution) - Collège de France
35 IGMM - MRC Institute of Genetics and Molecular Medicine [Edinburgh]
Gillian Rice
Guillaume Thouvenin


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.
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hal-03228789 , version 1 (19-02-2024)




Marie-Louise Frémond, Alice Hadchouel, Laureline Berteloot, Isabelle Melki, Violaine Bresson, et al.. Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients. Journal of Allergy and Clinical Immunology: In Practice, 2021, 9 (2), pp.803-818.e11. ⟨10.1016/j.jaip.2020.11.007⟩. ⟨hal-03228789⟩
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