Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jun 4;14(1):35.
doi: 10.1186/s12969-016-0094-4.

Type I interferonopathies in pediatric rheumatology

Stefano Volpi  1 , Paolo Picco  1 , Roberta Caorsi  1 , Fabio Candotti  2 , Marco Gattorno  3
Affiliations
Review

Type I interferonopathies in pediatric rheumatology

Stefano Volpi et al. Pediatr Rheumatol Online J. .

Abstract

Defective regulation of type I interferon response is associated with severe inflammatory phenotypes and autoimmunity. Type I interferonopathies are a clinically heterogenic group of Mendelian diseases with a constitutive activation of this pathway that might present as atypical, severe, early onset rheumatic diseases. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common. Recent studies have implicated abnormal responses to nucleic acid stimuli or defective regulation of downstream effector molecules in disease pathogenesis. As observed for IL1-β and autoinflammatory diseases, knowledge of the defects responsible for type I interferonopathies will likely promote the development of targeted therapy.

Keywords: Aicardi-Goutières syndrome; CANDLE; Familial lupus; SAVI; Type I interferon; Type I interferonopathies.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Cytoplasmic nucleic acid recognition and type I IFN pathway activation. Scheme of cytoplasmic nucleotide sensing, type I IFN secretion and autocrine and paracrine IFNAR activation. Colored in blue are some of the proteins mutated in type I interferonopathies. Pathways currently not fully understood are identified with a question mark. cGAMP: cyclic di-GMP-AMP, cGAS: cyclic GMP-AMP synthase, ER: endothelial reticulum, ERGIC: endothelial reticulum-Golgi intermediate compartment, IFIH1: IFN-induced helicase C domain-containing protein 1 (also known as MDA5), IFNAR: interferon-α receptor, ISG15: interferon-stimulated gene 15, MAVS: mitochondrial antiviral-signaling protein, RIG-I: retinoic acid-inducible gene 1, SAMHD1: deoxynucleoside triphosphate triphosphohydrolase SAM domain and HD domain 1, STING: stimulator of interferon genes, TBK1: TANK-binding kinase 1, TREX1: DNA 3ʹ repair exonuclease 1, USP18: ubiquitin-specific protease 18
Fig. 2
Fig. 2
Clinical presentation and blood interferon signature of a SAVI patient. Purpuric plaques with ulcerative evolution (panel a), onychodystrophy (panel b), CT scan revealing focal thickening of the interlobular septa with areas of ground glass opacities (panel c), and peripheral blood type I interferon signature (panel d) (assessed as described [67]) in a patient with SAVI syndrome
See this image and copyright information in PMC

References

    1. Crow YJ. Type I, interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci. 2011;1238:91–8. doi: 10.1111/j.1749-6632.2011.06220.x. - DOI - PubMed
    1. Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147(927):258–67. doi: 10.1098/rspb.1957.0048. - DOI - PubMed
    1. Cavlar T, Ablasser A, Hornung V. Induction of type I IFNs by intracellular DNA-sensing pathways. Immunol Cell Biol. 2012;90(5):474–82. doi: 10.1038/icb.2012.11. - DOI - PubMed
    1. McGlasson S, Jury A, Jackson A, Hunt D. Type I interferon dysregulation and neurological disease. Nat Rev Neurol. 2015;11(9):515–23. doi: 10.1038/nrneurol.2015.143. - DOI - PubMed
    1. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339(6121):826–30. doi: 10.1126/science.1229963. - DOI - PMC - PubMed

MeSH terms

Supplementary concepts