{"id":63748,"date":"2026-05-09T12:00:00","date_gmt":"2026-05-09T10:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/05\/09\/tofacitinib-as-a-successful-treatment-for-hyper-ige-syndrome-and-autoimmunity-associated-with-constitutive-activation-of-jak3\/"},"modified":"2026-05-09T12:00:00","modified_gmt":"2026-05-09T10:00:00","slug":"tofacitinib-as-a-successful-treatment-for-hyper-ige-syndrome-and-autoimmunity-associated-with-constitutive-activation-of-jak3","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/05\/09\/tofacitinib-as-a-successful-treatment-for-hyper-ige-syndrome-and-autoimmunity-associated-with-constitutive-activation-of-jak3\/","title":{"rendered":"Tofacitinib as a Successful Treatment for Hyper-IgE Syndrome and Autoimmunity Associated with Constitutive Activation of JAK3"},"content":{"rendered":"<div>\n<p><b>J Clin Immunol<\/b>. 2026 May 9. doi: 10.1007\/s10875-026-02027-9. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>The Janus Kinase 3 (JAK3) germline gain-of-function (GOF) mutation is a rare inborn error of immunity, first reported in 2020, characterized by lymphopenia and chronic NK-cell proliferation. However, its role in autoimmunity remains unclear, and no direct association with hyper-IgE syndrome (HIES) has been established. In this study, we describe a patient presenting with HIES, myositis, lymphopenia, and autoimmune hypothyroidism. Whole-exome sequencing identified a novel compound heterozygous JAK3 mutation (c.2524_2525delinsTT and c.2805G &gt; C), predicted to be deleterious. Flow cytometry and RNA sequencing of peripheral blood mononuclear cells revealed a significant reduction in T cells and NK cells, particularly na\u00efve CD4<sup>+<\/sup> T cells, accompanied by a marked imbalance in T cell subsets. This led to constitutive activation of JAK1 and JAK3, along with increased STAT3 and STAT5 phosphorylation. Tofacitinib treatment significantly improved the patient&#8217;s symptoms. Our findings expand the clinical spectrum of JAK3-associated immune dysregulation, linking it for the first time to HIES and multiple autoimmune manifestations. Furthermore, this study suggests that tofacitinib may be a potential therapeutic option for JAK3 signaling-associated immune dysregulation.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42105147\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_campaign=journals&amp;utm_content=8102137&amp;ff=20260510061513&amp;v=2.20.0\">42105147<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1007\/s10875-026-02027-9\">10.1007\/s10875-026-02027-9<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Clin Immunol. 2026 May 9. doi: 10.1007\/s10875-026-02027-9. Online ahead of print. ABSTRACT The Janus Kinase 3 (JAK3) germline gain-of-function (GOF) mutation is a rare inborn error of immunity, first reported in 2020, characterized by lymphopenia and chronic NK-cell proliferation. However, its role in autoimmunity remains unclear, and no direct association with hyper-IgE syndrome (HIES) &#8230; <a title=\"Tofacitinib as a Successful Treatment for Hyper-IgE Syndrome and Autoimmunity Associated with Constitutive Activation of JAK3\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/05\/09\/tofacitinib-as-a-successful-treatment-for-hyper-ige-syndrome-and-autoimmunity-associated-with-constitutive-activation-of-jak3\/\" aria-label=\"Read more about Tofacitinib as a Successful Treatment for Hyper-IgE Syndrome and Autoimmunity Associated with Constitutive Activation of JAK3\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-63748","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/63748","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=63748"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/63748\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=63748"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=63748"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=63748"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}