Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Targeting the mTOR pathway in idiopathic multicentric Castleman disease
Robert M. Stern, Nancy Berliner
Robert M. Stern, Nancy Berliner
Published September 16, 2019
Citation Information: J Clin Invest. 2019;129(10):4086-4088. https://doi.org/10.1172/JCI131332.
View: Text | PDF
Commentary

Targeting the mTOR pathway in idiopathic multicentric Castleman disease

  • Text
  • PDF
Abstract

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic illness of systemic inflammation and organ dysfunction, with unknown etiology. Although therapies targeting IL-6 have been proven effective, a subset of patients with iMCD are resistant to this approach. In this issue of the JCI, Fajgenbaum et al. performed an in-depth analysis of serum inflammatory markers in three iMCD patients refractory to IL-6 blockade, and identified activation of the mTOR pathway associated with symptom flares. Treatment with sirolimus, an mTOR inhibitor, induced remission in all three patients. This study models a precision medicine approach to discovering therapies for rare diseases.

Authors

Robert M. Stern, Nancy Berliner

×

Figure 1

Inhibition of the IL-6 and mTOR pathways in iMCD influences symptoms.

Options: View larger image (or click on image) Download as PowerPoint
Inhibition of the IL-6 and mTOR pathways in iMCD influences symptoms.
IL...
IL-6 and IL-6 receptor (IL-6R) associate with the signal transducer gp130, leading to dimerization and activation of the JAK/STAT signaling cascade. Siltuximab neutralizes IL-6 and tocilizumab blocks the IL-6R. Growth factor (GF) binds to the receptor tyrosine kinase (RTK) leading to downstream activation of PI3 kinase (PI3K), AKT, and ultimately mTOR. Sirolimus binds to the tacrolimus binding protein (FKBP), and together sirolimus and FKBP inhibit mTOR activity.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts