伴有JAK2V617F突变的缺血性脑血管病患者的血栓炎症

Thromboinflammation in ischemic cerebrovascular patients with the JAK2V617F mutation.

作者信息

Kristiansen Marie Hvelplund, Larsen Morten Kranker, Massarenti Laura, Skov Vibe, Kjær Lasse, Enevold Christian, Ostrowski Sisse Rye, Nielsen Claus Henrik, Hasselbalch Hans Carl, Wienecke Troels

机构信息

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Neurology, Zealand University Hospital, Roskilde, Denmark.

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Hematology, Zealand University Hospital, Roskilde, Denmark.

出版信息

Thromb Res. 2025 Jan;245:109236. doi: 10.1016/j.thromres.2024.109236. Epub 2024 Dec 6.

DOI:10.1016/j.thromres.2024.109236

PMID:39652998

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.

摘要

背景

JAK2V617F突变是费城染色体阴性骨髓增殖性肿瘤（MPN）的驱动因素，也与心血管疾病有关。MPN中的血栓形成涉及JAK2V617F相关的血小板活化和内皮功能障碍，所有这些都可能受慢性炎症影响。该突变在非MPN患者中是否同样影响血栓炎症标志物尚不清楚。

方法

我们开展了一项研究，纳入63例携带JAK2V617F突变的缺血性脑血管病患者，并与63例未携带该突变的患者进行匹配。在急性期和随访3个月时分析血清样本中的12种血栓炎症标志物。

结果

总体而言，病例组和对照组的血栓炎症标志物无显著差异。然而，对JAK2V617F等位基因负担≥1%的患者（n = 15）进行亚组分析显示，与对照组相比，基线时血管细胞黏附分子-1（VCAM-1）水平较高（p = 0.018），随访时白细胞介素-10（IL-10）（p = 0.004）和肿瘤坏死因子α（TNF-α）（p = 0.018）升高。回归分析显示，较高的JAK2V617F等位基因负担与基线时VCAM-1升高（p < 0.001）以及随访时较高的VCAM-1（p = 0.012）、IL-10（p = 0.003）和TNF-α（p = 0.034）相关。