{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:40:27Z","timestamp":1790746827196,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601753"],"award-info":[{"award-number":["81601753"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      TYK2 deficiency is a rare primary immunodeficiency disease caused by loss\u2010of\u2010function mutations of\n                      <jats:italic>TYK2<\/jats:italic>\n                      gene, which is initially proposed as a subset of hyper\u2010IgE syndrome (HIES). However, accumulating evidence suggests TYK2\u2010deficient patients do not necessarily present with HIES characteristics, indicating a vacuum of knowledge on the exact roles of TYK2 in human immune system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Pathogenic effects of patients were confirmed by qRT\u2010PCR, Western blot, and protein stability assays. The responses to cytokines including IFN\u2010\u03b1\/\u03b2\/\u03b3, IL\u20106, IL\u201010, IL\u201012, and IL\u201023 of peripheral blood mononuclear cells (PBMCs) from these patients were detected by Western blot, qRT\u2010PCR, and flow cytometry. The differentiation of T and B cells was detected by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We described five more TYK2\u2010deficient cases presenting with or without hyper\u2010IgE levels, atopy, and distinct pathogen infection profile, which are caused by novel\n                      <jats:italic>TYK2<\/jats:italic>\n                      mutations. These mutations were all found by high\u2010throughput sequencing and confirmed by Sanger sequencing. The patients showed heterogeneous responses to various cytokine treatments, including IFN\u2010\u03b1\/\u03b2\/\u03b3, IL\u20106, IL\u201010, IL\u201012, and IL\u201023. The homeostasis of lymphocytes is also disrupted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on our findings, we propose that TYK2 works as a multi\u2010tasker in orchestrating various cytokine signaling pathways, differentially combined defects which account for the expressed clinical manifestations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.13671","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T19:59:10Z","timestamp":1632772750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Novel mutations of TYK2 leading to divergent clinical 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