Overview of STING-associated vasculopathy with onset in infancy (SAVI) among 21 patients
ML Frémond, A Hadchouel, L Berteloot, I Melki… - The Journal of Allergy …, 2021 - Elsevier
ML Frémond, A Hadchouel, L Berteloot, I Melki, V Bresson, L Barnabei, N Jeremiah, A Belot…
The Journal of Allergy and Clinical Immunology: In Practice, 2021•ElsevierBackground 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 …
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 …
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.
Elsevier
