tetano
Editor, Senior Moderator
RMD Open
. 2025 Oct 5;11(4):e005231.
doi: 10.1136/rmdopen-2024-005231. Polyclonal Vβ21.3 expansion in multisystem inflammatory syndrome in children despite SARS-CoV-2 vaccination
Stejara Netea[SUP] #[/SUP][SUP] 1 2 [/SUP], Liliane Khoryati[SUP] #[/SUP][SUP] 3 [/SUP], Sietse Nagelkerke[SUP] #[/SUP][SUP] 4 5 [/SUP], Sarah Benezech[SUP] 3 [/SUP], Jim Keijser[SUP] 6 [/SUP], Mariken Gruppen[SUP] 4 [/SUP], Giske Biesbroek[SUP] 4 [/SUP], Roel Lubbers[SUP] 7 [/SUP], Naomi Ketharanathan[SUP] 8 [/SUP], Emilie Buddingh[SUP] 9 [/SUP], Nikki Schoenmaker[SUP] 10 [/SUP], Arianne Brandsma[SUP] 11 [/SUP], Theo Rispens[SUP] 6 12 [/SUP], Irene Kuipers[SUP] 13 [/SUP], Alexandre Belot[SUP] 3 14 [/SUP], Taco Kuijpers[SUP] 4 5 [/SUP]
Affiliations
Multisystem inflammatory syndrome in children (MIS-C) is a severe SARS-CoV-2-associated condition that shares clinical features with Kawasaki disease (KD), characterised by a distinct polyclonal expansion of Vβ21.3+ T cells. We report five patients diagnosed with breakthrough MIS-C despite COVID-19 immunisation, all within a limited time period at the beginning of the Omicron wave, to assess whether breakthrough MIS-C cases share the same TCR Vβ21.3 skewing seen in non-vaccinated MIS-C cases. We retrospectively reviewed five MIS-C patients hospitalised between December 2021 and April 2022 despite previous immunisation against SARS-CoV-2 (BNT162b2, an mRNA vaccine against S-protein). Immunophenotyping, including TCR Vβ subset distribution, was performed in four patients.Patients (100% male, 12.2-17.2 years) had a natural breakthrough SARS-CoV-2 infection following prior immunisation (between August 2021 and February 2022). Recent infection was proven by positive SARS-CoV-2 PCR and/or IgG antibodies against the nucleocapsid protein. Blood samples of four patients were available. All presented with Vβ21.3+ T cell expansion, similar to MIS-C patients and in contrast to vaccinated historical KD patients (n=10). The two patients with the earliest sampling post-illness displayed frequencies of Vβ21.3+ T cells exceeding the reference mean value+10×SD. These Vβ21.3+ T cells showed increased surface expression of activation (HLA-DR, CD38) and exhaustion (PD-1, TIM-3) markers.In conclusion, breakthrough MIS-C patients presented with features consistent with unvaccinated MIS-C patients, including the hallmark Vβ21.3+ T cell expansion, indicating that prior immunisation with an mRNA vaccine targeting the Wuhan strain did not fully protect against MIS-C at the wave of a novel emerging variant early 2022. Trial registration number: NL41023.018.12.
Keywords: Inflammation; T-Lymphocytes; Vaccination.
. 2025 Oct 5;11(4):e005231.
doi: 10.1136/rmdopen-2024-005231. Polyclonal Vβ21.3 expansion in multisystem inflammatory syndrome in children despite SARS-CoV-2 vaccination
Stejara Netea[SUP] #[/SUP][SUP] 1 2 [/SUP], Liliane Khoryati[SUP] #[/SUP][SUP] 3 [/SUP], Sietse Nagelkerke[SUP] #[/SUP][SUP] 4 5 [/SUP], Sarah Benezech[SUP] 3 [/SUP], Jim Keijser[SUP] 6 [/SUP], Mariken Gruppen[SUP] 4 [/SUP], Giske Biesbroek[SUP] 4 [/SUP], Roel Lubbers[SUP] 7 [/SUP], Naomi Ketharanathan[SUP] 8 [/SUP], Emilie Buddingh[SUP] 9 [/SUP], Nikki Schoenmaker[SUP] 10 [/SUP], Arianne Brandsma[SUP] 11 [/SUP], Theo Rispens[SUP] 6 12 [/SUP], Irene Kuipers[SUP] 13 [/SUP], Alexandre Belot[SUP] 3 14 [/SUP], Taco Kuijpers[SUP] 4 5 [/SUP]
Affiliations
- PMID: 41052890
- DOI: 10.1136/rmdopen-2024-005231
Multisystem inflammatory syndrome in children (MIS-C) is a severe SARS-CoV-2-associated condition that shares clinical features with Kawasaki disease (KD), characterised by a distinct polyclonal expansion of Vβ21.3+ T cells. We report five patients diagnosed with breakthrough MIS-C despite COVID-19 immunisation, all within a limited time period at the beginning of the Omicron wave, to assess whether breakthrough MIS-C cases share the same TCR Vβ21.3 skewing seen in non-vaccinated MIS-C cases. We retrospectively reviewed five MIS-C patients hospitalised between December 2021 and April 2022 despite previous immunisation against SARS-CoV-2 (BNT162b2, an mRNA vaccine against S-protein). Immunophenotyping, including TCR Vβ subset distribution, was performed in four patients.Patients (100% male, 12.2-17.2 years) had a natural breakthrough SARS-CoV-2 infection following prior immunisation (between August 2021 and February 2022). Recent infection was proven by positive SARS-CoV-2 PCR and/or IgG antibodies against the nucleocapsid protein. Blood samples of four patients were available. All presented with Vβ21.3+ T cell expansion, similar to MIS-C patients and in contrast to vaccinated historical KD patients (n=10). The two patients with the earliest sampling post-illness displayed frequencies of Vβ21.3+ T cells exceeding the reference mean value+10×SD. These Vβ21.3+ T cells showed increased surface expression of activation (HLA-DR, CD38) and exhaustion (PD-1, TIM-3) markers.In conclusion, breakthrough MIS-C patients presented with features consistent with unvaccinated MIS-C patients, including the hallmark Vβ21.3+ T cell expansion, indicating that prior immunisation with an mRNA vaccine targeting the Wuhan strain did not fully protect against MIS-C at the wave of a novel emerging variant early 2022. Trial registration number: NL41023.018.12.
Keywords: Inflammation; T-Lymphocytes; Vaccination.