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  • Perspective
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A path towards personalized medicine for autoinflammatory and related diseases

Nature Reviews Rheumatology volume 19, pages 182–189 (2023)Cite this article

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Abstract

The human genome project led to the advancement of genetic technologies and genomic medicine for a variety of human diseases, including monogenic autoimmune and autoinflammatory diseases. As a result, the genome of an individual can now be rapidly sequenced at a low cost, and this technology is beginning to change the practice of rheumatology. In this Perspective, we describe how new sequencing technologies combined with careful clinical phenotyping have led to the discovery of rare rheumatic diseases and their corresponding disease-causing mutations. Additionally, we explore ways in which single-gene mutations, including somatic mutations, are creating opportunities to develop personalized medicines. To illustrate this idea, we focus on diseases affecting the TREX1–cGAS–STING pathway, which is associated with monogenic autoinflammatory diseases and vasculopathies. For many of the affected patients and families, there is an urgent, unmet need for the development of personalized therapies. New innovations related to small molecular inhibitors and gene therapies have the potential to benefit these families, and might help drive further innovations that could prove useful for patients with more common forms of autoimmunity and autoinflammation.

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Fig. 1: The evolution of DNA sequencing technology.
Fig. 2: Rare rheumatic diseases and the TREX1–cGAS–STING pathway.
Fig. 3: The discovery of RVCL and subsequent search for a cure.

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Acknowledgements

The authors would like to thank E. Roberson for helpful discussions about genome sequencing technology.

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Authors and Affiliations

  1. Departments of Medicine and Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Jonathan J. Miner

  2. Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Katherine A. Fitzgerald

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  1. Jonathan J. Miner
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  2. Katherine A. Fitzgerald
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The authors contributed equally to all aspects of the article.

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Correspondence to Jonathan J. Miner or Katherine A. Fitzgerald.

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Nature Reviews Rheumatology thanks S. Masters and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Miner, J.J., Fitzgerald, K.A. A path towards personalized medicine for autoinflammatory and related diseases. Nat Rev Rheumatol 19, 182–189 (2023). https://doi.org/10.1038/s41584-022-00904-2

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