Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Proteínas de Membrana/genética , Dermatopatias Vasculares/diagnóstico , Doenças Vasculares/diagnóstico , Idade de Início , Anemia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Anticorpos Antinucleares/imunologia , Artralgia/tratamento farmacológico , Artralgia/genética , Artralgia/imunologia , Sedimentação Sanguínea , Bronquiectasia/diagnóstico , Bronquiectasia/tratamento farmacológico , Bronquiectasia/genética , Bronquiectasia/imunologia , Proteína C-Reativa/imunologia , Pré-Escolar , Tosse , Insuficiência de Crescimento , Feminino , Febre/tratamento farmacológico , Febre/genética , Febre/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Lactente , Interferon Tipo I , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/imunologia , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/tratamento farmacológico , Nódulos Pulmonares Múltiplos/genética , Nódulos Pulmonares Múltiplos/imunologia , Osteoartropatia Hipertrófica Primária , Análise de Sequência de DNA , Proteína Amiloide A Sérica , Dermatopatias Vasculares/tratamento farmacológico , Dermatopatias Vasculares/genética , Dermatopatias Vasculares/imunologia , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/genética , Doenças Vasculares/imunologiaRESUMO
OBJECTIVES: Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib. METHODS: We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis. RESULTS: We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease. CONCLUSIONS: We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.