Journal article
Overview of STING-associated vasculopathy with onset in infancy (SAVI) among 21 patients.
- Frémond ML Université de Paris, Paris, France; Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France; Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France.
- Hadchouel A Université de Paris, Paris, France; Pediatric Pulmonology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; INEM, INSERM U1151, Paris, France.
- Berteloot L Pediatric Radiology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France.
- Melki I Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France; Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; General Pediatrics- Infectious Diseases and Internal Medicine Department, Hôpital Robert Debré, AP-HP.Nord-Université de Paris, Paris, France.
- Bresson V Pediatric Emergency Department, Hôpital de la Timone, AP-HM, Centre Hospitalier Universitaire de Marseille, Marseille, France.
- Barnabei L INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric Autoimmunity, Imagine Institute, Paris, France.
- Jeremiah N Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France.
- Belot A Pediatric Rheumatology, Nephrology and Dermatology Department, Hospices Civils de Lyon, Lyon, France; CIRI, Centre International de Recherche en Infectiologie, INSERM, U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon, France.
- Bondet V Translational Immunology Lab, Institut Pasteur, Paris, France.
- Brocq O Rheumatology Department, Centre Hospitalier Princesse Grace, Monaco, Monaco.
- Chan D Pediatric Allergy and Immunology Department, Women's and Children's Hospital, Adelaide, South Australia, Australia.
- Dagher R Department of Pediatrics, Notre Dame des Secours University Hospital, Jbeil, Lebanon.
- Dubus JC Pediatric Pulmonology Department, Hôpital de la Timone, AP-HM, Centre Hospitalier Universitaire de Marseille, Marseille, France.
- Duffy D Translational Immunology Lab, Institut Pasteur, Paris, France.
- Feuillet-Soummer S Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie-Lannelongue Hospital, Paris-Sud University, Le Plessis Robinson, France.
- Fusaro M Université de Paris, Paris, France; Study Center for Primary Immunodeficiencies, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; INSERM UMR 1163, Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Imagine Institute, Paris, France.
- Gattorno M Center for Autoinflammatory diseases and Immunodeficiencies, IRCCS Giannina Gaslini Institute, Genova, Italy.
- Insalaco A Pediatric Rheumatology Unit, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
- Jeziorski E Pediatrics Department, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
- Kitabayashi N Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France.
- Lopez-Corbeto M Pediatric Rheumatology Unit, Rheumatology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.
- Mazingue F Pediatric Hematology Department, Centre Hospitalier Universitaire de Lille, Lille, France.
- Morren MA Dermatology Department, University Hospitals Leuven, Leuven, Belgium; University hospital Lausanne and University of Lausanne Pediatric Dermatology Unit, Department of Pediatrics and Dermatol-Venereology, Lausanne, Switzerland.
- Rice GI Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PT, United Kingdom.
- Rivière JG Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Catalonia Spain; Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Catalonia, Spain; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain.
- Seabra L Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France.
- Sirvente J Internal Medecine Department, Hôpital Saint-Eloi, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
- Soler-Palacin P Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Catalonia Spain; Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Catalonia, Spain; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain.
- Stremler-Le Bel N Pediatric Pulmonology Department, Hôpital de la Timone, AP-HM, Centre Hospitalier Universitaire de Marseille, Marseille, France.
- Thouvenin G Pediatric Pulmonology Department and Reference center for rare lung disease RespiRare, Trousseau University Hospital, AP-HP. Sorbonne Université, Paris, France.
- Thumerelle C Pediatric Pneumology Department, Hôpital Jeanne de Flandre, CHRU Lille, Lille, France.
- VAN Aerde E Dermatology Department, University Hospitals Leuven, Leuven, Belgium.
- Volpi S Center for Autoinflammatory diseases and Immunodeficiencies, IRCCS Giannina Gaslini Institute, Genova, Italy.
- Willcocks S Pediatric Immunology and Allergy Service, Queensland Children's Hospital, Children's Health Queensland, Brisbane, Queensland, Australia.
- Wouters C Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; Pediatrics Department, University Hospitals Leuven, Leuven, Belgium; Department of Immunology and Microbiology- Childhood Immunology University of Leuven, Leuven, Belgium.
- Breton S Pediatric Radiology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France.
- Molina T Université de Paris, Paris, France; Pathology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France.
- Bader-Meunier B Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric Autoimmunity, Imagine Institute, Paris, France.
- Moshous D Université de Paris, Paris, France; Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Imagine Institute, Paris, France.
- Fischer A Université de Paris, Paris, France; Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; INSERM UMR 1163, Imagine Institute, Paris, France; Collège de France, Paris, France.
- Blanche S Université de Paris, Paris, France; Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France.
- Rieux-Laucat F Université de Paris, Paris, France; INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric Autoimmunity, Imagine Institute, Paris, France.
- Crow YJ Université de Paris, Paris, France; Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France; Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: yanickcrow@mac.com.
- Neven B Université de Paris, Paris, France; Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP.Centre Université de Paris, Paris, France; INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric Autoimmunity, Imagine Institute, Paris, France. Electronic address: benedicte.neven@aphp.fr.
- 2020-11-20
Published in:
- The journal of allergy and clinical immunology. In practice. - 2020
JAK inhibitors
STING1
Stimulator of interferon genes
interstitial lung disease
lymphopenia
polyarthritis
type I interferonopathy
vasculopathy
English
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 SAVI patients.
METHODS
Assessment of clinical, radiological, and immunologic data from 21 patients (17 families).
RESULTS
Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most patients were symptomatic from infancy but late onset in adulthood occurred in one 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 one infant mimicked a combined immune deficiency. Extended features reminiscent of other interferonopathies were also found e.g. intracranial calcification, glaucoma, 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 benefice of ruxolitinib in SAVI unless the treatment is started early in the course of the disease underlying the need for early diagnosis. Tolerance was reasonably good.
CONCLUSION
This largest worldwide cohort of SAVI patients precise core features and extends the clinical and immunological phenotype of the disease, displaying overlap with other monogenic interferonopathies.
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 SAVI patients.
METHODS
Assessment of clinical, radiological, and immunologic data from 21 patients (17 families).
RESULTS
Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most patients were symptomatic from infancy but late onset in adulthood occurred in one 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 one infant mimicked a combined immune deficiency. Extended features reminiscent of other interferonopathies were also found e.g. intracranial calcification, glaucoma, 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 benefice of ruxolitinib in SAVI unless the treatment is started early in the course of the disease underlying the need for early diagnosis. Tolerance was reasonably good.
CONCLUSION
This largest worldwide cohort of SAVI patients precise core features and extends the clinical and immunological phenotype of the disease, displaying overlap with other monogenic interferonopathies.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.jaip.2020.11.007
- PMID 33217613
- Persistent URL
- https://folia.unifr.ch/global/documents/44760
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