{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:27:21Z","timestamp":1790393241810,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":246,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Autoimmune polyglandular syndrome type\u20101 (APS\u20101) is a monogenic recessive disorder characterised by multiple endocrine abnormalities, chronic mucocutaneous candidiasis and high titres of serum autoantibodies. To date, no curative treatment is available; current therapies manage the symptoms rather than treating the cause and have major side effects. APS\u20101 is caused by mutations in the autoimmune regulator (<jats:italic>AIRE<\/jats:italic>) gene. AIRE mediates central tolerance by directing the ectopic expression of tissue\u2010specific antigens (TSAs) in medullary thymic epithelial cells, causing the deletion of self\u2010reactive thymocytes. Therefore, loss\u2010of\u2010function mutations in <jats:italic>AIRE<\/jats:italic> result in a multisystem autoimmune disease. Because of the monogenic aetiology of APS\u20101 and availability of an APS\u20101 mouse model, we have explored the option of restoring functional AIRE using adeno\u2010associated virus serotype 9 (AAV9).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The efficacy of AAV9\u2010AIRE (AAV9 carrying AIRE cDNA) gene therapy was assessed in an APS\u20101 mouse model. We performed intrathymic injection of AAV9\u2010AIRE into APS\u20101 mouse model using ultrasound imaging technique to accurately locating the thymus. We evaluated the efficiency of this approach alongside measures of autoimmunity and histology of target tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intrathymic injection of AAV9\u2010AIRE demonstrated high transduction efficiency and restored AIRE expression in the thymus. AIRE gene delivery led to a significant increase in TSA expression, and importantly a significant reduction of serum autoantibodies in treated versus control mice, which fell to near\u2010undetectable levels by 4\u00a0weeks post\u2010treatment. Furthermore, histological analysis of treated animals showed near\u2010normal tissue morphology with no lymphocytic infiltrations, a hallmark of untreated <jats:italic>Aire\u2010<\/jats:italic>deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study has demonstrated the feasibility of AAV9\u2010AIRE as a vehicle for gene therapy for APS\u20101.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1166","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:03:09Z","timestamp":1599177789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["AAV9\u2010mediated AIRE gene delivery clears circulating antibodies and tissue T\u2010cell infiltration in a mouse model of autoimmune polyglandular syndrome type\u20101"],"prefix":"10.1002","volume":"9","author":[{"given":"Sarah","family":"Almaghrabi","sequence":"first","affiliation":[{"name":"Department of 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