Thromboinflammation in ischemic cerebrovascular patients with the JAK2V617F mutation
Marie Hvelplund Kristiansen a), b, Morten Kranker Larsen a), c), Laura Massarenti d), e), Vibe Skov c), Lasse Kjær c), Christian Enevold e), Sisse Rye Ostrowski a), f), Claus Henrik Nielsen d), e), Hans Carl Hasselbalch a), c), Troels Wienecke a), b)
a) Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
b) Department of Neurology, Zealand University Hospital, Roskilde, Denmark
c) Department of Hematology, Zealand University Hospital, Roskilde, Denmark
d) Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
e) Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
f) Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Abstract
Background
The JAK2V617F mutation is a driver of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) and is also implicated in cardiovascular diseases. Thrombosis in MPN involves JAK2V617F-associated platelet activation and endothelial dysfunction, all potentially influenced by chronic inflammation. Whether the mutation affects thromboinflammatory markers similarly in non-MPN patients remains unclear.
Method
We conducted a study involving 63 ischemic cerebrovascular patients with the JAK2V617F mutation, matched with 63 patients without the mutation. Serum samples were analyzed for 12 thromboinflammatory markers during the acute phase and at three months follow-up.
Results
Overall, there was no significant difference in thromboinflammatory markers between cases and controls. However, subgroup analysis of patients with a JAK2V617F allele burden ≥1 % (n = 15) showed higher levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) at baseline (p = 0.018), and elevated Interleukin-10 (IL-10) (p = 0.004) and Tumor Necrosis Factor α (TNF-α) (p = 0.018) at follow-up compared to controls. Regression analysis revealed an association between higher JAK2V617F allele burden and increased VCAM-1 at baseline (p < 0.001), and higher VCAM-1 (p = 0.012), IL-10 (p = 0.003), and TNF-α (p = 0.034) at follow-up.
Conclusion
In ischemic cerebrovascular patients, the JAK2V617F mutation is associated with elevated markers of endothelial dysfunction and chronic inflammation. This underscores the role of inflammation in thrombosis driven by the JAK2V617F mutation.