Stimulator of Interferon Genes–Associated Vasculitis of Infancy

Omoyinmi, Ebun; Gomes, Sónia; Nanthapisal, Sira; Woo, Patricia; Standing, Ariane; Eleftheriou, Despina; Klein, Nigel; Brogan, Paul A.

doi:10.1002/art.38998

Cited by 45 publications

(39 citation statements)

References 3 publications

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“…Early mortality due to respiratory failure likely related to underlying SAVI lung disease often in the context of infections is seen [4, 26, 27]. See Table 1 for details.…”

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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“…Early mortality due to respiratory failure likely related to underlying SAVI lung disease often in the context of infections is seen [4, 26, 27]. See Table 1 for details.…”

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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“…The STING/IFNβ pathway can be directly activated in endothelial cells indicating that the development of vasculitis may be triggered directly by dermal endothelial cell activation [2, 3]**,**. Because STING coordinates signals from multiple upstream dsDNA sensors, it may be a target for therapeutic interventions not only in SAVI, but also in a wider variety of IFN-mediated diseases [2-4]. …”

Section: Introductionmentioning

confidence: 99%

Newly recognized Mendelian disorders with rheumatic manifestations

Jesús

Goldbach‐Mansky

2015

Current Opinion in Rheumatology

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“…Twenty-two patients from 15 families have been reported with heterozygous GOF mutations in TMEM173 involving amino acids at positions 147, 154, 155, and 166 localized near (V147L) or within the dimerization domain (DD; N154S, V155M, and G166E) of STING protein. 15,16,[19][20][21][22][23][24] These changes have been suggested to lead to stabilization of the DD and thus constitutive activation of STING. 15,16 Three other patients with SAVI have been described, carrying distinct mutations (namely C206Y in exon 6 and R281Q and R284G in exon 7) located in the cGAMP binding domain of STING that also lead to constitutive activation of the protein, thereby implicating a second region of STING important in type I interferon signaling.…”

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confidence: 99%