JAK inhibitor withdrawal causes a transient pro-inflammatory cascade: A potential mechanism for major adverse cardiac events
Type I JAKinibs paradoxically accumulate functionally defective pJAK. Upon withdrawal, the primed pJAKs are de-repressed and initiate a pSTAT signaling cascade, resulting in high interferon and urokinase. Type II JAKinibs do not cause pJAK accumulation, pSTAT cascade, and subsequent pro-inflammatory transcripts. The resultant cytokines and proteins produced from this cascade might explain adverse cardiac outcomes. Thus, JAKinib withdrawal is a possible mechanism contributing to the major adverse cardiac events described with JAKinib therapy.
Authors
- Gaëtane Nocturne (ORCID: https://orcid.org/0000-0001-6809-0733)
- Loïc Meudec (ORCID: https://orcid.org/0000-0001-6322-8801)
- Ilya Gurevic
- Xavier Mariette (ORCID: https://orcid.org/0000-0002-4244-5417)
- Sara S. McCoy (ORCID: https://orcid.org/0000-0002-5293-4185)
Institutions
- University of Wisconsin–Madison (US)
- Inserm (FR)
- Université Paris-Saclay (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Infectious Disease Models and Innovative Therapies (FR)
- Bicêtre Hospital (FR)
Publication Details
- Journal
- PLoS ONE
- Published
- 2025-06-16
- DOI
- https://doi.org/10.1371/journal.pone.0311706
- Citations
- 1
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Pfizer Foundation
- National Institute of Dental and Craniofacial Research
- National Center for Advancing Translational Sciences