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Neuropathologic Impacts of JAK Inhibitor Treatment in Aicardi-Goutières Syndrome

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Abstract

Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by upregulation of type I interferon response. It is associated with increased mortality and severe disabilities. Janus Kinase (JAK) inhibitors have shown effectiveness in treatment of AGS through blocking the downstream effects of interferon activation. We illustrate post-mortem histopathologic findings in a patient with AGS who received baricitinib treatment for a duration of over 4 years, initiating at a remarkably young age of 2 months. We observed global cerebral atrophy, markedly diminished white matter, abundant calcifications involving supratentorial white matter, basal ganglia, dentate nuclei, and brainstem. This study showed profound central nervous system (CNS) sequelae despite early initiation of treatment. Our findings highlight the potential necessity for therapeutic options with enhanced CNS bioavailability.

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Fig. 1

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No datasets were generated or analysed during the current study.

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Funding

The authors received no external funding for the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Division of Neurology, Department of Pediatrics, Children’s Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA

    Saba Jafarpour & Jonathan D. Santoro

  2. Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Saba Jafarpour & Jonathan D. Santoro

  3. Department of Pathology, LA General Medical Center, Los Angeles, CA, USA

    Jolee Suddock

  4. Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Jolee Suddock & Debra Hawes

  5. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Debra Hawes

Authors
  1. Saba Jafarpour
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  2. Jolee Suddock
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  3. Debra Hawes
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  4. Jonathan D. Santoro
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Contributions

S.J. wrote the main manuscript text and prepared figure S1; J.D.S, J.T.S. and D.H. contributed to the main text; J.T.S. and D.H. prepared Fig. 1, figure S2, and table S1. All authors reviewed the manuscript.

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Correspondence to Saba Jafarpour.

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The authors declare no competing interests.

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Jafarpour, S., Suddock, J., Hawes, D. et al. Neuropathologic Impacts of JAK Inhibitor Treatment in Aicardi-Goutières Syndrome. J Clin Immunol 44, 68 (2024). https://doi.org/10.1007/s10875-024-01672-2

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  • DOI: https://doi.org/10.1007/s10875-024-01672-2

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