{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:34:54Z","timestamp":1791480894759,"version":"4.3.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009702","name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico","doi-asserted-by":"publisher","award":["FOGS-2021, Ricerca Corrente , Liver BIBLE (PR-0361)"],"award-info":[{"award-number":["FOGS-2021, Ricerca Corrente , Liver BIBLE (PR-0361)"]}],"id":[{"id":"10.13039\/501100009702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2016-02364358 , RF-2021-12373889 , PNRR-MAD-2022-12375656"],"award-info":[{"award-number":["RF-2016-02364358 , RF-2021-12373889 , PNRR-MAD-2022-12375656"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["grant agreement No. 777377, grant agreement \u201c101096312\u201d"],"award-info":[{"award-number":["grant agreement No. 777377, grant agreement \u201c101096312\u201d"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PNRR \u2013 M4 - C2 , PRIN 2022 , PNC-E3-2022-23683266 - \u2018INNOVA\u2019 , Dipartimenti di Eccellenza Program 2023 to 2027"],"award-info":[{"award-number":["PNRR \u2013 M4 - C2 , PRIN 2022 , PNC-E3-2022-23683266 - \u2018INNOVA\u2019 , Dipartimenti di Eccellenza Program 2023 to 2027"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multisystem inflammatory syndrome in children (MIS-C) is an uncommon delayed complication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children, whose cause remains unknown. The aim of this study was to investigate the role of genetic predisposition to COVID-19 and dysregulated inflammatory response in the development of MIS-C in Italian children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eighteen individuals were enrolled: 12 with classical MIS-C and 6 with a Kawasaki\u2013SARS-CoV-2-related disease (KD). The frequency distribution of the main common risk variants underpinning COVID-19 susceptibility (\n                      <jats:italic>ABO<\/jats:italic>\n                      tagging SNPs) and severity (five GWAS-prioritized loci) was compared between patients and children with COVID-19 without MIS-C and with adult controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 79 and\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a02,848, respectively). Whole exome sequencing (WES) was performed in the MIS-C cohort to examine the frequency of rare damaging variants in a panel of 207 immune-related genes as compared to that of local controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 266).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Blood group B alleles conferred an increased risk of MIS-C independently of sex, ethnicity, the presence of COVID-19, and blood group A [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.04\u20138.5;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.04], with a larger impact on the KD subphenotype (OR 6.8; 95% CI 1.7\u201335.1;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.007). A total of 49 rare damaging variants, 4 classified as pathogenic, were prioritized in 39 immune-related genes; all patients harbored at least one variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results not only support a role of blood group B as a risk factor for MIS-C development in children with COVID-19, possibly through modulation of the coagulability and microvascular dysfunction, but also support an immune-genetic basis for this condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1777516","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:05:04Z","timestamp":1775801104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of blood group B and of rare variants affecting immune system with multisystem inflammatory syndrome in children in an Italian cohort"],"prefix":"10.3389","volume":"17","author":[{"given":"Luisa","family":"Ronzoni","sequence":"first","affiliation":[{"name":"Precisione Medicine Lab, Biological Resource Center and Department of Transfusion Medicine, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada Maria","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Pediatric Emergency Department, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Precisione Medicine Lab, Biological Resource Center and Department of Transfusion Medicine, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Miano","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Minoia","sequence":"additional","affiliation":[{"name":"Pediatric Immuno-Rheumatology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Baselli","sequence":"additional","affiliation":[{"name":"Pediatric Immuno-Rheumatology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Filocamo","sequence":"additional","affiliation":[{"name":"Pediatric Immuno-Rheumatology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Torcianti","sequence":"additional","affiliation":[{"name":"Precisione Medicine Lab, Biological Resource Center and Department of Transfusion Medicine, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Malvestiti","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Bosis","sequence":"additional","affiliation":[{"name":"Pneumology and Infectious Diseases Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, 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