Stimulator of Interferon Genes–Associated Vasculopathy With Onset in Infancy

Muñoz, J; Rodière, M.; Jeremiah, Nadia; Rieux-Laucat, Frédéric; Oojageer, Anthony; Rice, Gillian I.; Rozenberg, Flore; Crow, Yanick J.; Bessis, Didier

doi:10.1001/jamadermatol.2015.0251

Cited by 106 publications

(104 citation statements)

References 14 publications

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“…All STING mutations described to date are localised within the dimerisation domain and are associated with fever episodes and interstitial pulmonary disease, in addition to signs of peripheral vasculitis 12 13 19. In contrast, symptoms of patients with familial chilblain lupus carrying the G166E mutation are confined to the skin, although systemic involvement is evident from an increased expression of IFN-stimulated genes in blood and formation of antinuclear antibodies.…”

Section: Discussionmentioning

confidence: 99%

Familial chilblain lupus due to a gain-of-function mutation in STING

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Familial chilblain lupus due to a gain-of-function mutation in STING

et al. 2016

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“…Features of vascular and/or tissue damage include nail dystrophy, gangrene/infarcts of fingers/toes with tissue loss, and nasal septal perforation [4, 26–28]. In lesional skin biopsy endothelial cells, there is upregulation of endothelial inflammation (inducible nitric oxide synthase), coagulation (tissue factor), and endothelial cell adhesion and activation (E-selectin).…”

Section: Clinical and Pathogenic Description Of The Mendelian (Monogementioning

confidence: 99%

Insights from Mendelian Interferonopathies: Comparison of CANDLE, SAVI with AGS, Monogenic Lupus

2016

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Autoinflammatory disorders are sterile inflammatory conditions characterized by episodes of early-onset fever and disease-specific patterns of organ inflammation. Recently, the discoveries of monogenic disorders with strong type I interferon (IFN) signatures caused by mutations in proteasome degradation and cytoplasmic RNA and DNA sensing pathways suggest a pathogenic role of IFNs in causing autoinflammatory phenotypes. The IFN response gene signature (IGS) has been associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. In this review, we compare the clinical presentations and pathogenesis of two IFN-mediated autoinflammatory diseases, CANDLE and SAVI, with Aicardi Goutières syndrome (AGS) and monogenic forms of SLE (monoSLE) caused by loss-of-function mutations in complement 1 (C1q) or the DNA nucleases, DNASE1 and DNASE1L3. We outline differences in intracellular signaling pathways that fuel a pathologic type I IFN amplification cycle. While IFN amplification is caused by predominantly innate immune cell dysfunction in SAVI, CANDLE, and AGS, autoantibodies to modified RNA and DNA antigens interact with tissues and immune cells including neutrophils and contribute to IFN upregulation in some SLE patients including monoSLE, thus justifying a grouping of “autoinflammatory” and “autoimmune” interferonopathies. Understanding of the differences in the cellular sources and signaling pathways will guide new drug development and the use of emerging targeted therapies.

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“…So far disease-causing missense mutations affect three amino acids, V155, N154 V147 [2-5]. Patients present with early-onset vasculitis/vasculopathy that affects small dermal vessels in mostly acral areas leading to vasoocclusion and gangrene often requiring surgical amputation.…”

Section: Introductionmentioning

confidence: 99%

“…Patients present with early-onset vasculitis/vasculopathy that affects small dermal vessels in mostly acral areas leading to vasoocclusion and gangrene often requiring surgical amputation. Most patients also develop progressive interstitial lung disease (ILD) with variable severity [2-5]. Elevated autoantibody levels are seen in these patients, however the titers do not correlate with the presence or severity of the vascultis and lung disease [2]**.…”

Section: Introductionmentioning

confidence: 99%