{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:17:56Z","timestamp":1787235476372,"version":"build-2736575974"},"reference-count":155,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Elevated serum IgE levels serve as a critical marker for uncovering hidden immunological disorders, particularly inborn errors of immunity (IEIs), which are often misdiagnosed as common allergic conditions. IgE, while typically associated with allergic diseases, plays a significant role in immune defense, especially against parasitic infections. However, extremely high levels of IgE can indicate more severe conditions, such as Hyper-IgE syndromes (HIES) and disorders with similar features, including Omenn syndrome, Wiskott-Aldrich syndrome, and IPEX syndrome. Novel insights into the genetic mutations responsible for these conditions highlight their impact on immune regulation and the resulting clinical features, including recurrent infections, eczema, and elevated IgE. This narrative review uniquely integrates recent advances in the genetic understanding of IEIs and discusses how these findings impact both diagnosis and treatment. Additionally, emerging therapeutic strategies, such as hematopoietic stem cell transplantation (HSCT) and gene therapies, are explored, underscoring the potential for personalized treatment approaches. Emphasizing the need for precise diagnosis and tailored interventions aims to enhance patient outcomes and improve the quality of care for those with elevated IgE levels and associated immunological disorders.<\/jats:p>","DOI":"10.3390\/life14101329","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T06:46:52Z","timestamp":1729234012000},"page":"1329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4166-2030","authenticated-orcid":false,"given":"Francesca","family":"Galletta","sequence":"first","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-0903","authenticated-orcid":false,"given":"Antonella","family":"Gambadauro","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Foti Randazzese","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4369-7798","authenticated-orcid":false,"given":"Stefano","family":"Passanisi","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Sinatra","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Caminiti","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Zirilli","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-8411","authenticated-orcid":false,"given":"Sara","family":"Manti","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Human Pathology in Adult and Developmental Age \u2018Gaetano Barresi\u2019, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0021-8707(66)90091-8","article-title":"Physicochemical Properties of Reaginic Antibody. 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