The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench

Markus J Hofer; Nicholson Modesti; Nicole G Coufal; Qingde Wang; Sunetra Sase; Jonathan J Miner; Adeline Vanderver; Mariko L Bennett

doi:10.1111/imr.13413

The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench

Immunol Rev. 2024 Oct 29. doi: 10.1111/imr.13413. Online ahead of print.

Authors

Markus J Hofer¹, Nicholson Modesti², Nicole G Coufal^{3

4

5}, Qingde Wang⁶, Sunetra Sase², Jonathan J Miner⁷, Adeline Vanderver^{2

8}, Mariko L Bennett^{2

8}

Affiliations

¹ Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, New South Wales, Australia.
² Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
³ Department of Pediatrics, University of California, San Diego, California, USA.
⁴ Rady Children's Hospital, San Diego, California, USA.
⁵ Sanford Consortium for Regenerative Medicine, San Diego, California, USA.
⁶ Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
⁷ Department of Medicine and Microbiology, RVCL Research Center, and Colton Center for Autoimmunity, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
⁸ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 39473130
DOI: 10.1111/imr.13413

Abstract

Aicardi-Goutières syndrome (AGS) is a progressive genetic encephalopathy caused by pathogenic mutations in genes controlling cellular anti-viral responses and nucleic acid metabolism. The mutations initiate autoinflammatory processes in the brain and systemically that are triggered by chronic overproduction of type I interferon (IFN), including IFN-alpha. Emerging disease-directed therapies aim to dampen autoinflammation and block cellular responses to IFN production, creating an urgent and unmet need to understand better which cells, compartments, and mechanisms underlying disease pathogenesis. In this review, we highlight existing pre-clinical models of AGS and our current understanding of how causative genetic mutations promote disease in AGS, to promote new model development and a continued focus on improving and directing future therapies.

Keywords: Aicardi‐Goutieres; Type I interferon; cytokines; inflammation; interferonopathy; leukodystrophy; neuroimmunology.

Publication types

Review

Abstract

Publication types

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