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.


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*


  • Janus Kinase Inhibitors

Supplementary concepts

  • Aicardi-Goutieres syndrome