{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T07:47:00Z","timestamp":1782200820032,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Inborn errors of immunity (\n                      <jats:styled-content style=\"fixed-case\">IEIs<\/jats:styled-content>\n                      ) affecting thymic cell development or function can result in thymic aplasia or hypoplasia, autoimmunity, and the generation of neutralizing autoantibodies (Auto\u2010Abs) targeting type I interferons (\n                      <jats:styled-content style=\"fixed-case\">IFNs<\/jats:styled-content>\n                      ) (\n                      <jats:styled-content style=\"fixed-case\">AAN<\/jats:styled-content>\n                      \u2010I\u2010\n                      <jats:styled-content style=\"fixed-case\">IFNs<\/jats:styled-content>\n                      ).\n                      <jats:styled-content style=\"fixed-case\">FOXN1<\/jats:styled-content>\n                      is a master transcriptional regulator of thymic epithelial cells and the impact of the\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>FOXN1<\/jats:italic>\n                      <\/jats:styled-content>\n                      variants spans a spectrum from pathogenic to benign. In pediatric patients with heterozygous\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>FOXN1<\/jats:italic>\n                      <\/jats:styled-content>\n                      variants the full spectrum of clinical and immunological determinants remains to be defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using a luminex multiplex immunoassay, we assessed the presence of auto\u2010Abs against 14 cytokines. We then employed two complementary in\u00a0vitro cellular assays to test the neutralizing capacity of circulating auto\u2010Abs against type I\n                      <jats:styled-content style=\"fixed-case\">IFNs<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here, we present the case of an 11\u2010year\u2010old child who presented at 20\u2009days of age with multiple severe infections. Genetic analysis revealed a heterozygous\n                      <jats:italic>FOXN1<\/jats:italic>\n                      variant: c.1448_1451del. The patient tested positive for auto\u2010Abs against type I IFNs. Functional assays confirmed the presence of auto\u2010Abs with neutralizing activity against IFN\u2010\u03b12 (at both low [10\u2009ng\/mL] and high [50\u2009ng\/mL] concentrations) and against IFN\u2010\u03c9 (only at 0.1\u2009ng\/mL and 10\u2009ng\/mL), but not against IFN\u2010\u03b2. Five months later, following four doses of rituximab, circulating autoantibodies levels decreased by about 60%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclutions<\/jats:title>\n                    <jats:p>\n                      These findings suggest that heterozygous\n                      <jats:italic>FOXN1<\/jats:italic>\n                      variants can impair thymic development in a manner that promotes the selective emergence of neutralizing auto\u2010Abs against type I IFNs, thereby predisposing affected individuals to severe viral infections. Monitoring these auto\u2010Abs may support personalized therapeutic strategies for affected patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.70314","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T04:25:04Z","timestamp":1773462304000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutralizing autoantibodies against IFN\u2010\u03b12 and IFN\u2010\u03c9 in a boy with a heterozygous variant in the\n                    <i>FOXN1<\/i>\n                    gene"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5559-2654","authenticated-orcid":false,"given":"Arturo","family":"Guti\u00e9rrez\u2010Guerrero","sequence":"first","affiliation":[{"name":"Immune Deficiencies Laboratory, Instituto Nacional de Pediatr\u00eda Secretar\u00eda de Salud  Mexico City 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