tetano
Editor, Senior Moderator
Med
. 2024 Mar 15:S2666-6340(24)00080-1.
doi: 10.1016/j.medj.2024.02.008. Online ahead of print. The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination
Hing Wai Tsang[SUP] 1 [/SUP], Mike Yat Wah Kwan[SUP] 1 [/SUP], Gilbert T Chua[SUP] 1 [/SUP], Sabrina Siu Ling Tsao[SUP] 1 [/SUP], Joshua Sung Chih Wong[SUP] 2 [/SUP], Keith Tsz Suen Tung[SUP] 1 [/SUP], Godfrey Chi Fung Chan[SUP] 3 [/SUP], Kelvin Kai Wang To[SUP] 4 [/SUP], Ian Chi Kei Wong[SUP] 5 [/SUP], Wing Hang Leung[SUP] 6 [/SUP], Patrick Ip[SUP] 7 [/SUP]
Affiliations
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[SUP]+[/SUP] NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57[SUP]+[/SUP] 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).
Keywords: BNT162b2 mRNA COVID-19 vaccines; KIR genetics; NK cells; Translation to patients; hypercytokinemia; inflammation; innate immunity; vaccine-related myocarditis.
. 2024 Mar 15:S2666-6340(24)00080-1.
doi: 10.1016/j.medj.2024.02.008. Online ahead of print. The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination
Hing Wai Tsang[SUP] 1 [/SUP], Mike Yat Wah Kwan[SUP] 1 [/SUP], Gilbert T Chua[SUP] 1 [/SUP], Sabrina Siu Ling Tsao[SUP] 1 [/SUP], Joshua Sung Chih Wong[SUP] 2 [/SUP], Keith Tsz Suen Tung[SUP] 1 [/SUP], Godfrey Chi Fung Chan[SUP] 3 [/SUP], Kelvin Kai Wang To[SUP] 4 [/SUP], Ian Chi Kei Wong[SUP] 5 [/SUP], Wing Hang Leung[SUP] 6 [/SUP], Patrick Ip[SUP] 7 [/SUP]
Affiliations
- PMID: 38521068
- DOI: 10.1016/j.medj.2024.02.008
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[SUP]+[/SUP] NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57[SUP]+[/SUP] 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).
Keywords: BNT162b2 mRNA COVID-19 vaccines; KIR genetics; NK cells; Translation to patients; hypercytokinemia; inflammation; innate immunity; vaccine-related myocarditis.