Neuropathologic Impacts of JAK Inhibitor Treatment in Aicardi-Goutières Syndrome

Saba Jafarpour; Jolee Suddock; Debra Hawes; Jonathan D Santoro

doi:10.1007/s10875-024-01672-2

Neuropathologic Impacts of JAK Inhibitor Treatment in Aicardi-Goutières Syndrome

J Clin Immunol. 2024 Feb 21;44(3):68. doi: 10.1007/s10875-024-01672-2.

Authors

Saba Jafarpour^{1

2}, Jolee Suddock^{3

4}, Debra Hawes^{4

5}, Jonathan D Santoro^{6

7}

Affiliations

¹ Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA. [email protected].
² Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [email protected].
³ Department of Pathology, LA General Medical Center, Los Angeles, CA, USA.
⁴ Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁵ Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶ Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
⁷ Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

PMID: 38381212
DOI: 10.1007/s10875-024-01672-2

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.

Publication types

Letter

MeSH terms

Autoimmune Diseases of the Nervous System* / drug therapy
Autoimmune Diseases of the Nervous System* / genetics
Disease Progression
Humans
Infant
Janus Kinase Inhibitors* / therapeutic use
Nervous System Malformations*

Substances

Janus Kinase Inhibitors

Supplementary concepts

Aicardi-Goutieres syndrome