{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:02:22Z","timestamp":1787166142817,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Inherited chronic mucocutaneous candidiasis (CMC) is often caused by inborn errors of immunity, impairing the response to, or the production of IL\u201017A and IL\u201017F. About half of the cases carry\n                      <jats:italic>STAT1<\/jats:italic>\n                      \u00a0gain\u2010of\u2010function (GOF) mutations. Only few patients have been reported with mutations of\n                      <jats:italic>TRAF3IP2<\/jats:italic>\n                      , a gene encoding the adaptor ACT1 essential for IL\u201017 receptor(R) signaling. We investigated a 10\u2010year\u2010old girl with CMC, carrying a heterozygous variant of\n                      <jats:italic>STAT1<\/jats:italic>\n                      and compound heterozygous variants of\n                      <jats:italic>TRAF3IP2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      By flow cytometry, STAT1\u00a0levels and phosphorylation (CD14+) as well as IL\u201017A, IL\u201022, IFN\u2010\u03b3, and IL\u20104 production (memory CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells) were determined. ACT1 expression and binding to IL\u201017RA were assessed by Western blot and co\u2010immunoprecipitation in HEK\u2010293T cells transfected with plasmids encoding wild\u2010type or mutant HA\u2010tagged ACT1 and Flag\u2010IL\u201017RA. We evaluated IL\u201017A responses by measuring luciferase induction under a NF\u2010\u03baB\u2010driven reporter system in HEK\u2010293T cells and Gro\u2010\u03b1 secretion in fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A\n                      <jats:italic>STAT1<\/jats:italic>\n                      variant (c.1363G&gt;A\/p.V455I) was identified by next\u2010generation sequencing and classified as likely non\u2010pathogenic as functional testing revealed normal STAT1 expression and phosphorylation upon IFN\u2010\u03b3. We also found compound heterozygous variants (c.1325A&gt;G\/p.D451G and c.1335delA\/p.K454fs11*) of\n                      <jats:italic>TRAF3IP2<\/jats:italic>\n                      . By overexpression, despite normal protein expression, and impaired (K454fs11*) or normal (D451G) interaction with IL\u201017RA, both mutant alleles resulted in impaired NF\u2010\u03baB activation. Patient's fibroblasts displayed abolished GRO\u2010\u03b1 secretion upon IL\u201017A stimulation. Finally, ex vivo CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells showed increased IL\u201017A, IL\u201022, and IL\u20104 and normal low IFN\u2010\u03b3 expression upon stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We identify novel compound heterozygous variants of\n                      <jats:italic>TRAFP3IP2<\/jats:italic>\n                      causing autosomal recessive ACT1 deficiency in a child with CMC and provide a review of the current literature.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.13603","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T15:03:25Z","timestamp":1626879805000},"page":"1804-1812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Biallelic TRAF3IP2 variants causing chronic mucocutaneous candidiasis in a child harboring a STAT1 variant"],"prefix":"10.1111","volume":"32","author":[{"given":"Pilar","family":"Blanco Lobo","sequence":"first","affiliation":[{"name":"Pediatric Infectious Diseases, Rheumatology and Immunology Unit Hospital Universitario Virgen del Roc\u00edo Instituto de Biomedicina de Sevilla IBiS\/ Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Traslacional en Infectolog\u00eda Pedi\u00e1trica RITIP Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Te","family":"Lei","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch The Rockefeller University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Pelham","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch The Rockefeller University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Guisado Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases, Rheumatology and Immunology Unit Hospital Universitario Virgen del Roc\u00edo Instituto de Biomedicina de Sevilla IBiS\/ Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Traslacional en Infectolog\u00eda Pedi\u00e1trica RITIP Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Villaoslada","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases, Rheumatology and Immunology Unit Hospital Universitario Virgen del Roc\u00edo Instituto de Biomedicina de Sevilla IBiS\/ Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Traslacional en Infectolog\u00eda Pedi\u00e1trica RITIP Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"de Felipe","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases, Rheumatology and Immunology Unit Hospital Universitario Virgen del Roc\u00edo Instituto de Biomedicina de Sevilla IBiS\/ Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Traslacional en Infectolog\u00eda Pedi\u00e1trica RITIP Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Lucena","sequence":"additional","affiliation":[{"name":"Immunology Unit. University Hospital Virgen del Roc\u00edo Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Laurent","family":"Casanova","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch The Rockefeller University New York NY USA"},{"name":"Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM Paris France"},{"name":"University of Paris Imagine Institute Paris France"},{"name":"Howard Hughes Medical Institute New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9853-7903","authenticated-orcid":false,"given":"Peter","family":"Olbrich","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases, Rheumatology and Immunology Unit Hospital Universitario Virgen del Roc\u00edo Instituto de Biomedicina de Sevilla IBiS\/ Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Traslacional en 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