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An Update on Autoinflammatory Diseases: Interferonopathies

  • Pediatric Rheumatology (S Ozen, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Type I interferons (IFNαβ) induce the expression of hundreds of genes; thus, it is unsurprising that the initiation, transmission, and resolution of the IFNαβ-mediated immune response is tightly controlled. Mutations that alter nucleic acid processing and recognition, ablate IFNαβ-specific negative feedback mechanisms, or result in dysfunction of the proteasome system can all induce pathogenic IFNαβ signalling and are the focus of this review.

Recent Findings

Recent advances have delineated the precise cytoplasmic mechanisms that facilitate self-DNA to be recognised by cGAS and self-RNA to be recognised by RIG-I or MDA-5. This helps clarify interferonopathies associated with mutations in genes which code for DNase-II and ADAR1, among others. Similarly, loss of function mutations in Pol α, which lowers the presence of antagonistic ligands in the cytosol, or gain of function mutations in RIG-I and MDA-5, result in increased propensity for receptor activation and therefore IFNαβ induction.

Summary

As the aetiology of monogenic autoinflammatory diseases are uncovered, novel and sometimes unsuspected molecular interactions and signalling pathways are being defined. This review covers developments that have come to light over the past 3 years, with reference to the study of interferonopathies.

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Acknowledgements

The authors would like to thank members of the Masters Lab, particularly Dr. Paul Baker and Dr. Fiona Moghaddas, for discussion and advice on this review.

Funding

S.L.M acknowledges funding from NHMRC grants (1144282, 1142354, and 1099262), The Sylvia and Charles Viertel Foundation, HHMI-Wellcome International Research Scholarship, and Glaxosmithkline. S.D. acknowledges funding from NHMRC ECF: GNT1143412.

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Authors and Affiliations

  1. Inflammation division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia

    Sophia Davidson, Annemarie Steiner, Cassandra R. Harapas & Seth L. Masters

  2. Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia

    Annemarie Steiner & Seth L. Masters

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  1. Sophia Davidson
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  2. Annemarie Steiner
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Correspondence to Sophia Davidson or Seth L. Masters.

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Conflict of Interest

Dr. Masters reports grants from NHMRC, grants from Viertel Foundation, grants from HHMI-Wellcome Trust, grants from Glaxosmithkline, outside the submitted work.

Dr. Davidson reports grants from NHMRC, outside the submitted work.

Drs. Steiner and Harapas declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Pediatric Rheumatology

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Davidson, S., Steiner, A., Harapas, C.R. et al. An Update on Autoinflammatory Diseases: Interferonopathies. Curr Rheumatol Rep 20, 38 (2018). https://doi.org/10.1007/s11926-018-0748-y

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