Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review
ABSTRACT Background and Aim Hyper IgE syndromes (HIES) are rare primary immunodeficiency characterized by susceptibility to specific infections, eczema, and elevated IgE levels. Pathogenic mutations in STAT3, IL6R, IL6ST, ERBB2IP, PGM3, ZNF431, SPINK5, TGFBR1/2, and CARD11 have been identified as ge...
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Wiley
2025-03-01
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| Series: | Health Science Reports |
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| Online Access: | https://doi.org/10.1002/hsr2.70497 |
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| author | Mohammad Salehi Zeinab Neshati Hamid Ahanchian Rana Tafrishi Alireza Pasdar Mojtaba Safi Ehsan Ghayoor Karimiani |
| author_facet | Mohammad Salehi Zeinab Neshati Hamid Ahanchian Rana Tafrishi Alireza Pasdar Mojtaba Safi Ehsan Ghayoor Karimiani |
| author_sort | Mohammad Salehi |
| collection | DOAJ |
| description | ABSTRACT Background and Aim Hyper IgE syndromes (HIES) are rare primary immunodeficiency characterized by susceptibility to specific infections, eczema, and elevated IgE levels. Pathogenic mutations in STAT3, IL6R, IL6ST, ERBB2IP, PGM3, ZNF431, SPINK5, TGFBR1/2, and CARD11 have been identified as genetic factors contributing to phenotypes of HIES lead to hindered differentiation and activity, aberrant signaling cascades and disrupting immune regulation. HIES present a diverse clinical symptoms, challenging diagnosis and management; understanding its pathophysiology, genetics, and immunological abnormalities offer hope for improved outcomes. In this review we aim to provide a comprehensive understanding of the condition and also discuss latest updates on pathological features, clinical spectrum and its variability, immunological abnormalities, inheritance patterns, new candidate genes, challenges, management strategies, epidemiology and future directions of HIES. Methods This review conducted an extensive search of information from multiple databases, including PubMed, Scopus, WHO, and ClinVar to ensure comprehensive coverage. Preference was given to articles published recently to capture the latest research and developments. Endnote was employed as a reference manager. The relevant literature was meticulously reviewed to address the objectives of the study. Results Missense, nonsense, and frameshift variants are commonly observed in HIES. Understanding these genetic mutations is key to diagnosing and managing conditions such as Hyper‐IgE recurrent infection syndromes (linked to IL6R, STAT3, and ZNF341 mutations), Atopy associated with ERBIN mutations which links STAT3 and TGF‐β pathway, Immunodeficiency 23 (caused by PGM3 mutations), Netherton syndrome (resulting from SPINK5 mutations), and Loeys‐Dietz syndrome (related to TGFBR mutations). Each year, new genes and variants responsible for this type of immune deficiency are added to the list. Conclusion Although rare, HIES significantly impacts patients due to its complex medical manifestations and need for lifelong management. Identifying casual variants is essential for effective clinical management of these complex conditions. |
| format | Article |
| id | doaj-art-9257ce24e0d44de093ccec9fb6facd16 |
| institution | OA Journals |
| issn | 2398-8835 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Health Science Reports |
| spelling | doaj-art-9257ce24e0d44de093ccec9fb6facd162025-08-20T02:10:31ZengWileyHealth Science Reports2398-88352025-03-0183n/an/a10.1002/hsr2.70497Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative ReviewMohammad Salehi0Zeinab Neshati1Hamid Ahanchian2Rana Tafrishi3Alireza Pasdar4Mojtaba Safi5Ehsan Ghayoor Karimiani6Department of Biology, Faculty of Science Ferdowsi University of Mashhad Mashhad IranDepartment of Biology, Faculty of Science Ferdowsi University of Mashhad Mashhad IranAllergy Research Center Mashhad University of Medical Sciences Mashhad IranAllergy Research Center Mashhad University of Medical Sciences Mashhad IranDepartment of Medical Genetics and Molecular Medicine, Faculty of Medicine Mashhad University of Medical Sciences Mashhad IranDepartment of Genetics Next Generation Genetic Polyclinic Mashhad IranDepartment of Genetics Next Generation Genetic Polyclinic Mashhad IranABSTRACT Background and Aim Hyper IgE syndromes (HIES) are rare primary immunodeficiency characterized by susceptibility to specific infections, eczema, and elevated IgE levels. Pathogenic mutations in STAT3, IL6R, IL6ST, ERBB2IP, PGM3, ZNF431, SPINK5, TGFBR1/2, and CARD11 have been identified as genetic factors contributing to phenotypes of HIES lead to hindered differentiation and activity, aberrant signaling cascades and disrupting immune regulation. HIES present a diverse clinical symptoms, challenging diagnosis and management; understanding its pathophysiology, genetics, and immunological abnormalities offer hope for improved outcomes. In this review we aim to provide a comprehensive understanding of the condition and also discuss latest updates on pathological features, clinical spectrum and its variability, immunological abnormalities, inheritance patterns, new candidate genes, challenges, management strategies, epidemiology and future directions of HIES. Methods This review conducted an extensive search of information from multiple databases, including PubMed, Scopus, WHO, and ClinVar to ensure comprehensive coverage. Preference was given to articles published recently to capture the latest research and developments. Endnote was employed as a reference manager. The relevant literature was meticulously reviewed to address the objectives of the study. Results Missense, nonsense, and frameshift variants are commonly observed in HIES. Understanding these genetic mutations is key to diagnosing and managing conditions such as Hyper‐IgE recurrent infection syndromes (linked to IL6R, STAT3, and ZNF341 mutations), Atopy associated with ERBIN mutations which links STAT3 and TGF‐β pathway, Immunodeficiency 23 (caused by PGM3 mutations), Netherton syndrome (resulting from SPINK5 mutations), and Loeys‐Dietz syndrome (related to TGFBR mutations). Each year, new genes and variants responsible for this type of immune deficiency are added to the list. Conclusion Although rare, HIES significantly impacts patients due to its complex medical manifestations and need for lifelong management. Identifying casual variants is essential for effective clinical management of these complex conditions.https://doi.org/10.1002/hsr2.70497hyper IgE syndromesinborn errors of immunityjob syndromeprimary immunodeficiency |
| spellingShingle | Mohammad Salehi Zeinab Neshati Hamid Ahanchian Rana Tafrishi Alireza Pasdar Mojtaba Safi Ehsan Ghayoor Karimiani Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review Health Science Reports hyper IgE syndromes inborn errors of immunity job syndrome primary immunodeficiency |
| title | Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review |
| title_full | Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review |
| title_fullStr | Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review |
| title_full_unstemmed | Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review |
| title_short | Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review |
| title_sort | hyper ige syndromes understanding management and future perspectives a narrative review |
| topic | hyper IgE syndromes inborn errors of immunity job syndrome primary immunodeficiency |
| url | https://doi.org/10.1002/hsr2.70497 |
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