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An Update on Autoinflammatory Diseases: Inflammasomopathies

  • Pediatric Rheumatology (S Ozen, Section Editor)
  • Published:
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Abstract

Purpose of Review

Autoinflammatory diseases are driven by abnormal innate immune activation. In the case of inflammasomopathies, these are all attributable to activation of an inflammasome complex, nucleated by an innate immune sensor such as NLRP3. This review will focus on recent advances that have helped to elucidate the role of three other sensors (NLRP1, NLRC4 and pyrin) which can also cause inflammasomopathies.

Recent Findings

Mutations in pyrin (S242R or E244K) destroy an inhibitory 14-3-3 binding site and result in the newly characterised disease pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Moreover, a separate autoinflammatory disease driven by mevalonate kinase deficiency leads to defective RhoGTPase prenylation and subsequent loss of pyrin S242R phosphorylation, suggesting a shared mechanism of disease. Other inflammasomes such as NLRP1 and NLRC4 have had novel mutations described recently, which inform about the specific domains required for activation and autoinhibition.

Summary

This review covers recent advances in the study of inflammasomopathies, focussing on gene discoveries that elucidate new pathogenic mechanisms.

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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. SD 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

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

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

    Annemarie Steiner & Seth L. Masters

Authors
  1. Cassandra R. Harapas
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  2. Annemarie Steiner
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Correspondence to Sophia Davidson or Seth L. Masters.

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This article is part of the Topical Collection on Pediatric Rheumatology

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Harapas, C.R., Steiner, A., Davidson, S. et al. An Update on Autoinflammatory Diseases: Inflammasomopathies. Curr Rheumatol Rep 20, 40 (2018). https://doi.org/10.1007/s11926-018-0750-4

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