Weiss-Tessbach Matthias, Haider Teresa, Gowran Aoife, Schubert Lorenz, Mühlbacher Jakob, Brankovic Jelena, Wahrmann Markus, Jilma Bernd, Boehm Thomas
Department of Clinical Pharmacology, Medical University Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University Vienna, Vienna, Austria.
Inflamm Res. 2025 Apr 29;74(1):71. doi: 10.1007/s00011-025-02032-5.
SARS-CoV-2 vaccines are recommended for mastocytosis patients. We describe clinical symptoms, chemokine, cytokine, metabolomic and lipidomic derangements in a systemic mastocytosis patient following mRNA-1273 booster vaccination.
Twenty-eight chemokines and cytokines, 41 amino acids and 16 lipid classes were quantified with state-of-the-art methods.
Mast cell activation (MCA) symptoms started 24 h after the mRNA-1273 booster vaccination with significant metabolic, lipidomic and cytokine derangements. Histamine concentrations peaked at life-threatening 18 ng/ml concomitant with high tryptase. Peak plasma IL-1Ra, IL-5, IL-6, IL-10, IL-11, CXCL10 and GM-CSF concentrations were elevated 54-, 4.9-, 85-, 54-, 6.1-, 19- and 6.4-fold respectively. Tocilizumab, an IL-6 receptor antagonist, was administered 6 h after admission, because of the highly elevated IL-6 concentrations. More than one year later IL-6 was highly elevated during another MCA attack likely caused by a PCR-proven SARS-CoV-2 infection and tocilizumab was again used. Clinical symptoms improved during the following 12 h similar to the vaccine booster MCA attack.
A mRNA-1273 first booster vaccination likely caused a delayed severe MCA attack with highly elevated Th-biased cytokines with metabolic and lipidomic derangements. Administration of an IL-6 receptor blocker during both MCA attacks might have shortened the duration of clinical symptoms.
推荐为肥大细胞增多症患者接种新型冠状病毒2疫苗。我们描述了一名系统性肥大细胞增多症患者在接种mRNA-1273加强疫苗后的临床症状、趋化因子、细胞因子、代谢组学和脂质组学紊乱情况。
采用先进方法对28种趋化因子和细胞因子、41种氨基酸和16类脂质进行定量分析。
mRNA-1273加强疫苗接种24小时后出现肥大细胞活化(MCA)症状,伴有明显的代谢、脂质组学和细胞因子紊乱。组胺浓度在达到危及生命的18 ng/ml时达到峰值,同时类胰蛋白酶水平较高。血浆中白细胞介素-1受体拮抗剂(IL-1Ra)、白细胞介素-5、白细胞介素-6、白细胞介素-10、白细胞介素-11、CXC趋化因子配体10(CXCL10)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的峰值浓度分别升高了54倍、4.9倍、85倍、54倍、6.1倍、19倍和6.4倍。由于白细胞介素-6浓度大幅升高,入院6小时后给予了白细胞介素-6受体拮抗剂托珠单抗。一年多后,在另一次可能由聚合酶链反应证实的新型冠状病毒2感染引起的MCA发作期间,白细胞介素-6再次大幅升高,再次使用了托珠单抗。在接下来的12小时内,临床症状有所改善,类似于疫苗加强接种后的MCA发作。
首次接种mRNA-1273加强疫苗可能引发了延迟性严重MCA发作,伴有Th偏向性细胞因子大幅升高以及代谢和脂质组学紊乱。在两次MCA发作期间给予白细胞介素-6受体阻滞剂可能缩短了临床症状的持续时间。