{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:56:40Z","timestamp":1768553800748,"version":"3.49.0"},"posted":{"date-parts":[[2022,9,2]]},"group-title":"Rheumatology","reference-count":7,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory condition that follows SARS-CoV2 infection or exposure in children. Clinical presentations are highly variable and include fever, gastrointestinal (GI) disease, shock, and Kawasaki Disease-like illness (MIS-C\/KD). Compared to patients with acute COVID, patients with MIS-C have a distinct immune signature and expansion of\n                  <jats:italic>TRVB11<\/jats:italic>\n                  expressing T cells. However, the relationship between immunological and clinical phenotypes of MIS-C is unknown. Here, we measured serum biomarkers, TCR repertoire, and SARS-CoV2-specific T cell responses in a cohort of 76 MIS-C patients. Serum biomarkers associated with macrophage and Th1 activation were elevated in patients with shock, consistent with previous reports. Significantly increased SARS-CoV-2-induced IFN-\u03b3, IL-2, and TNF-\u03b1 production were seen in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells from patients with neurologic involvement and respiratory failure. Diarrhea was associated with a significant reduction in shock-associated serum biomarkers, suggesting a protective effect.\n                  <jats:italic>TRVB11<\/jats:italic>\n                  usage was highly associated with MIS-C\/KD and coronary aneurysms, suggesting a potential biomarker for these manifestations in MIS-C patients. By identifying novel immunologic associations with the different clinical phenotypes of MIS-C, this study provides insights into the clinical heterogeneity of MIS-C. These unique immunophenotypic associations could provide biomarkers to identify patients at risk for severe complications of MIS-C, including shock and MIS-C\/KD.\n                <\/jats:p>","DOI":"10.1101\/2022.08.31.22279265","type":"posted-content","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T17:40:25Z","timestamp":1662140425000},"source":"Crossref","is-referenced-by-count":0,"title":["Deep immune profiling uncovers novel associations with clinical phenotypes of Multisystem Inflammatory Syndrome in Children (MIS-C)"],"prefix":"10.64898","author":[{"given":"Christopher","family":"Redmond","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moses M.","family":"Kitakule","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aran","family":"Son","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"McKella","family":"Sylvester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Sacco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ottavia","family":"Delmonte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Licciardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Castagnoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Poli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmin","family":"Espinoza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Astudillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina A.","family":"Montealegre Sanchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karyl","family":"Barron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Magliocco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"Dobbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cihan","family":"Oguz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen C.","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi D.","family":"Notarangelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela A.","family":"Frischmeyer-Guerrerio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniella M.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"7","key":"2022090504350619000_2022.08.31.22279265v1.1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S2352-4642(22)00100-6","article-title":"Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study","volume":"6","year":"2022","journal-title":"The Lancet Child & Adolescent Health"},{"issue":"4","key":"2022090504350619000_2022.08.31.22279265v1.2","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2020.09.016","article-title":"The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19","volume":"183","year":"2020","journal-title":"Cell"},{"key":"2022090504350619000_2022.08.31.22279265v1.3","doi-asserted-by":"crossref","unstructured":"Hoste L , Roels L , Naesens L , Bosteels V , Vanhee S , Dupont S , et al. TIM3+ TRBV11-2 T cells and IFNgamma signature in patrolling monocytes and CD16+ NK cells delineate MIS-C. J Exp Med. 2022;219(2).","DOI":"10.1084\/jem.20211381"},{"issue":"5","key":"2022090504350619000_2022.08.31.22279265v1.4","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/s41591-022-01724-3","article-title":"Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19","volume":"28","year":"2022","journal-title":"Nat Med"},{"issue":"1","key":"2022090504350619000_2022.08.31.22279265v1.5","doi-asserted-by":"crossref","first-page":"7222","DOI":"10.1038\/s41467-021-27544-6","article-title":"Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction","volume":"12","year":"2021","journal-title":"Nat Commun"},{"key":"2022090504350619000_2022.08.31.22279265v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92740-9"},{"key":"2022090504350619000_2022.08.31.22279265v1.7","doi-asserted-by":"crossref","unstructured":"Porritt RA , Paschold L , Rivas MN , Cheng MH , Yonker LM , Chandnani H , et al. HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children. J Clin Invest. 2021;131(10).","DOI":"10.1172\/JCI146614"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2022.08.31.22279265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:49:34Z","timestamp":1768488574000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2022.08.31.22279265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":7,"URL":"https:\/\/doi.org\/10.1101\/2022.08.31.22279265","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1136\/ard-2022-223269","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2022,9,2]]},"subtype":"preprint"}}