Novel interferonopathies associated with mutations in RIG-I like receptors. (June 2016)

• Record Type: Journal Article
• Authors: Buers, Insa; Nitschke, Yvonne; Rutsch, Frank
• Is Part Of: Cytokine & growth factor reviews. Volume 29:(2016)
• Page Start: 101
• Page End: 107
• Publication Date: 2016-06
• Subjects: Singleton-Merten -- Aicardi-Goutières -- SLE; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2016.03.005
• Languages: English
• ISSNs: 1359-6101

Abstract

Highlights: Interferonopathies reflect a newly recognised entity with increased type I interferon levels and overlapping phenotypes. In the attached review, we focus on the most recent discoveries of the genetic basis and pathomechanism of interferonopathies associated with mutations in RIG-I like cytoplasmic receptors for double stranded RNA. Mutations in IFIH1 and DDX58 lead to typical and atypical Singleton-Merten syndrome which show a considerable overlap with Aicardi-Goutières syndrome. Abstract: Type I interferonopathies are a relatively new class of inherited autoimmune disorders associated with an inborn elevated interferon response. Activation of cytosolic receptors which recognize viral double stranded RNA including the RIG-I (retinoic acid–inducible gene I) like receptors RIG-I and MDA5 (melanoma differentiation-associated gene 5) has been shown to induce the transcription of type I interferon genes. Within recent years, with the help of next generation sequencing techniques in syndromic families, mutations in the genes encoding for RIG-I and MDA5 have been identified to cause rare diseases including Aicardi-Goutières syndrome, Systemic Lupus Erythematosus in certain individuals as well as classic and atypical Singleton-Merten syndrome. Patients carrying mono-allelic mutations in MDA5 and RIG-I show constitutive activation of the RIG-I receptors and downstream signalling associated with increased type I interferon production. Although differing in the degree of phenotypic expression and severity, the phenotype of these "novel" diseases shows a considerable overlap reflecting their common pathogenetic pathway.