{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T13:11:17Z","timestamp":1767791477008,"version":"3.49.0"},"reference-count":25,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"le Centre de r\u00e9f\u00e9rence des rhumatismes inflammatoires, des interf\u00e9ronopathies et des maladies autoimmunes (RAISE)."},{"name":"ANR","award":["ANR-21-CE17-0064"],"award-info":[{"award-number":["ANR-21-CE17-0064"]}]},{"name":"ANR","award":["ANR-21-RHUS-08"],"award-info":[{"award-number":["ANR-21-RHUS-08"]}]},{"name":"Dutch Foundation Kind & Handicap"},{"DOI":"10.13039\/100018693","name":"HORIZON EUROPE","doi-asserted-by":"crossref","award":["01057100"],"award-info":[{"award-number":["01057100"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,7,30]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>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 V\u03b221.3+ 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 V\u03b221.3 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 V\u03b2 subset distribution, was performed in four patients.Patients (100% male, 12.2\u201317.2 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 V\u03b221.3+ T\u2009cell 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 V\u03b221.3+ T cells exceeding the reference mean value+10\u00d7SD. These V\u03b221.3+ 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 V\u03b221.3+ T\u2009cell 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.<\/jats:p>","DOI":"10.1136\/rmdopen-2024-005231","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:35:19Z","timestamp":1759732519000},"page":"e005231","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Polyclonal V\u03b221.3 expansion in multisystem inflammatory syndrome in children despite SARS-CoV-2 vaccination"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-4705","authenticated-orcid":false,"given":"Stejara","family":"Netea","sequence":"first","affiliation":[{"name":"Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Department of Experimental Immunology, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliane","family":"Khoryati","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sietse","family":"Nagelkerke","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Benezech","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Keijser","sequence":"additional","affiliation":[{"name":"Immunopathology, Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariken","family":"Gruppen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giske","family":"Biesbroek","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roel","family":"Lubbers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beatrix Hospital, Gorinchem, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Ketharanathan","sequence":"additional","affiliation":[{"name":"Department of Neonatal and Pediatric Intensive Care, Erasmus MC Sophia, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilie","family":"Buddingh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikki","family":"Schoenmaker","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit, Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianne","family":"Brandsma","sequence":"additional","affiliation":[{"name":"Department of HLA Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo","family":"Rispens","sequence":"additional","affiliation":[{"name":"Immunopathology, Sanquin Research, Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Infection & Immunity, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-5332","authenticated-orcid":false,"given":"Alexandre","family":"Belot","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Lyon, France"},{"name":"Pediatric Rheumatology Department, National Reference Centre for Rare Rheumatism, autoimmune diseases and interferonopathies (RAISE), National Reference Centre for Rare Autoinflammatory Diseases and Amyloidosis (CEREMAIA), ERN RITA, Hospices Civils de Lyon, Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taco","family":"Kuijpers","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,10,5]]},"reference":[{"key":"2026010700550491000_11.4.e005231.1","doi-asserted-by":"crossref","unstructured":"Moreews M , Le Gouge K , Khaldi-Plassart S , et al . 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