دورية أكاديمية
The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination.
| العنوان: | The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination. |
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| المؤلفون: | Tsang HW; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China., Kwan MYW; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China., Chua GT; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China., Tsao SSL; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China., Wong JSC; Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital Authority, Hong Kong SAR, China., Tung KTS; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China., Chan GCF; Paediatric Haematology & Oncology Centre, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China., To KKW; Department of Microbiology, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China., Wong ICK; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; School of Pharmacy, Medical Sciences Division, Macau University of Science and Technology, Macau SAR, China; School of Pharmacy, Aston University, Birmingham B4 7ET, England., Leung WH; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. Electronic address: leungwhf@hku.hk., Ip P; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. Electronic address: patricip@hku.hk. |
| المصدر: | Med (New York, N.Y.) [Med] 2024 Apr 12; Vol. 5 (4), pp. 335-347.e3. Date of Electronic Publication: 2024 Mar 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101769215 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-6340 (Electronic) Linking ISSN: 26666340 NLM ISO Abbreviation: Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York] : Cell Press, [2020]- |
| مواضيع طبية MeSH: | Myocarditis*/etiology , Myocarditis*/metabolism , COVID-19*/prevention & control, Male ; Adolescent ; Humans ; COVID-19 Vaccines/adverse effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Troponin T/metabolism ; Interferon-gamma/metabolism ; Killer Cells, Natural/metabolism ; Cytokines/metabolism ; Vaccination/adverse effects ; Receptors, KIR2DL5/metabolism |
| مستخلص: | Background: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. Methods: Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and T cells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. Findings: Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1β (IL-1β), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57 + NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57 + NK subset was particularly prominent in males and in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis. Conclusion: Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects. Funding: This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G). Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: BNT162b2 mRNA COVID-19 vaccines; KIR genetics; NK cells; Translation to patients; hypercytokinemia; inflammation; innate immunity; vaccine-related myocarditis |
| المشرفين على المادة: | 0 (COVID-19 Vaccines) 0 (RNA, Messenger) 0 (Troponin T) 82115-62-6 (Interferon-gamma) 0 (Cytokines) 0 (KIR2DL5B protein, human) 0 (Receptors, KIR2DL5) |
| تواريخ الأحداث: | Date Created: 20240323 Date Completed: 20240415 Latest Revision: 20240415 |
| رمز التحديث: | 20240415 |
| DOI: | 10.1016/j.medj.2024.02.008 |
| PMID: | 38521068 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2666-6340 |
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| DOI: | 10.1016/j.medj.2024.02.008 |