The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
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).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
|---|---|
| Enthalten in: |
Med (New York, N.Y.) - 5(2024), 4 vom: 12. Apr., Seite 335-347.e3 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tsang, Hing Wai [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.medj.2024.02.008 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370106512 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370106512 | ||
| 003 | DE-627 | ||
| 005 | 20240415233529.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240324s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.medj.2024.02.008 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1376.xml |
| 035 | |a (DE-627)NLM370106512 | ||
| 035 | |a (NLM)38521068 | ||
| 035 | |a (PII)S2666-6340(24)00080-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tsang, Hing Wai |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.04.2024 | ||
| 500 | |a Date Revised 15.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BNT162b2 mRNA COVID-19 vaccines | |
| 650 | 4 | |a KIR genetics | |
| 650 | 4 | |a NK cells | |
| 650 | 4 | |a Translation to patients | |
| 650 | 4 | |a hypercytokinemia | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a innate immunity | |
| 650 | 4 | |a vaccine-related myocarditis | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Troponin T |2 NLM | |
| 650 | 7 | |a Interferon-gamma |2 NLM | |
| 650 | 7 | |a 82115-62-6 |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a KIR2DL5B protein, human |2 NLM | |
| 650 | 7 | |a Receptors, KIR2DL5 |2 NLM | |
| 700 | 1 | |a Kwan, Mike Yat Wah |e verfasserin |4 aut | |
| 700 | 1 | |a Chua, Gilbert T |e verfasserin |4 aut | |
| 700 | 1 | |a Tsao, Sabrina Siu Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Joshua Sung Chih |e verfasserin |4 aut | |
| 700 | 1 | |a Tung, Keith Tsz Suen |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Godfrey Chi Fung |e verfasserin |4 aut | |
| 700 | 1 | |a To, Kelvin Kai Wang |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Ian Chi Kei |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Wing Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Ip, Patrick |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Med (New York, N.Y.) |d 2020 |g 5(2024), 4 vom: 12. Apr., Seite 335-347.e3 |w (DE-627)NLM314117954 |x 2666-6340 |7 nnns |
| 773 | 1 | 8 | |g volume:5 |g year:2024 |g number:4 |g day:12 |g month:04 |g pages:335-347.e3 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.medj.2024.02.008 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 5 |j 2024 |e 4 |b 12 |c 04 |h 335-347.e3 | ||