{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:20Z","timestamp":1785405560592,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,1]]},"group-title":"Allergy and Immunology","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["ERC-101221534"],"award-info":[{"award-number":["ERC-101221534"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"VIB Grand Challenge"},{"name":"CSL Behring"},{"name":"GENeHOPE fund"},{"name":"Intramural Research Program of the National Institutes of Health"},{"award":["1236923N"],"award-info":[{"award-number":["1236923N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"publisher"}]},{"award":["G0A1725N"],"award-info":[{"award-number":["G0A1725N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"publisher"}]},{"award":["G0AD025N"],"award-info":[{"award-number":["G0AD025N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/04cc1bd73","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI095983"],"award-info":[{"award-number":["R01AI095983"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancement of Translational Sciences","doi-asserted-by":"crossref","award":["UL1TR001866"],"award-info":[{"award-number":["UL1TR001866"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0420db125","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00d670121","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Laboratoire d\u2019Excellence Integrative - Biology of Emerging Infectious Diseases","award":["ANR-10-LABX-62-IBEID"],"award-info":[{"award-number":["ANR-10-LABX-62-IBEID"]}]},{"id":[{"id":"https:\/\/ror.org\/00cv9y106","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Molecular characterization of human monogenic inborn errors of T cell immunity provides both biological insights and medical progress. We report rare biallelic deleterious variants in\n                  <jats:italic>GTF3A<\/jats:italic>\n                  , encoding transcription factor IIIA (TFIIIA), a zinc-finger protein required for transcription and chaperoning of 5S ribosomal RNA (rRNA). These variants were identified in ten patients from eight unrelated families and eight countries presenting with either T\n                  <jats:sup>-<\/jats:sup>\n                  B\n                  <jats:sup>+<\/jats:sup>\n                  NK\n                  <jats:sup>+<\/jats:sup>\n                  severe combined immunodeficiency (SCID) or combined immune deficiency (CID), characterized by T cell lymphopenia and variable antibody deficiency. The\n                  <jats:italic>GTF3A<\/jats:italic>\n                  variants disrupt TFIIIA function through distinct mechanisms, including defective DNA binding, aberrant nuclear localization, and reduced protein stability compromising TFIIIA-mediated transcription and chaperoning of 5S rRNA. Using artificial thymic organoids derived from TFIIIA-deficient CD34\u207a progenitors, an early developmental arrest at the T cell commitment stage was documented\n                  <jats:italic>in vitro<\/jats:italic>\n                  . Zebrafish deficient for\n                  <jats:italic>gtf3aa<\/jats:italic>\n                  recapitulated the impaired thymocyte development\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Together, these findings establish TFIIIA deficiency as a novel cause of (S)CID, expanding the genetic and mechanistic landscape of inborn errors of T cell immunity and uncovering an essential role for TFIIIA in human adaptive immunity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One-sentence summary<\/jats:title>\n                  <jats:p>\n                    Biallelic\n                    <jats:italic>GTF3A<\/jats:italic>\n                    variants causing TFIIIA deficiency, which disrupts 5S rRNA transcription, represent a novel monogenic cause of (S)CID, unveiling a crucial role of TFIIIA in T cell development.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.01.26356670","type":"posted-content","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:35:12Z","timestamp":1782959712000},"source":"Crossref","is-referenced-by-count":0,"title":["Inherited human TFIIIA deficiency disrupts T cell development"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-1341","authenticated-orcid":false,"given":"Evi","family":"Duthoo","sequence":"first","affiliation":[{"name":"Primary Immunodeficiency Research Lab (PIRL), Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium"},{"name":"Center for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Center, ERN-RITA center, Ghent University Hospital, Ghent, Belgium"},{"name":"Belgium Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5392-6593","authenticated-orcid":false,"given":"Sueun","family":"Park","sequence":"additional","affiliation":[{"name":"Primary Immunodeficiency Research Lab (PIRL), Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium"},{"name":"Center for Primary Immunodeficiency Ghent, Jeffrey Modell 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