Publications
Detailed Information
Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Uzel, Gulbu | - |
dc.contributor.author | Sampaio, Elizabeth P. | - |
dc.contributor.author | Lawrence, Monica G. | - |
dc.contributor.author | Hsu, Amy P. | - |
dc.contributor.author | Hackett, Mary | - |
dc.contributor.author | Dorsey, Morna J. | - |
dc.contributor.author | Noel, Richard J. | - |
dc.contributor.author | Verbsky, James W. | - |
dc.contributor.author | Freeman, Alexandra F. | - |
dc.contributor.author | Janssen, Erin | - |
dc.contributor.author | Bonilla, Francisco A. | - |
dc.contributor.author | Pechacek, Joseph | - |
dc.contributor.author | Chandrasekaran, Prabha | - |
dc.contributor.author | Browne, Sarah K. | - |
dc.contributor.author | Agharahimi, Anahita | - |
dc.contributor.author | Gharib, Ahmed M. | - |
dc.contributor.author | Mannurita, Sara C. | - |
dc.contributor.author | Yim, Jae Joon | - |
dc.contributor.author | Gambineri, Eleonora | - |
dc.contributor.author | Torgerson, Troy | - |
dc.contributor.author | Tran, Dat Q. | - |
dc.contributor.author | Milner, Joshua D. | - |
dc.contributor.author | Holland, Steven M. | - |
dc.date.accessioned | 2024-08-08T01:43:36Z | - |
dc.date.available | 2024-08-08T01:43:36Z | - |
dc.date.created | 2021-05-14 | - |
dc.date.created | 2021-05-14 | - |
dc.date.issued | 2013-06 | - |
dc.identifier.citation | Journal of Allergy and Clinical Immunology, Vol.131 No.6, pp.1611-1623 | - |
dc.identifier.issn | 0091-6749 | - |
dc.identifier.uri | https://hdl.handle.net/10371/207628 | - |
dc.description.abstract | Background: Mutations in signal transducer and activator of transcription (STAT) 1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles) to mild disseminated mycobacterial disease (hypomorphic alleles) to chronic mucocutaneous candidiasis (CMC; hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity, and squamous cell cancers. Objective: We sought to investigate the role of STAT1 gain-of-function mutations in phenotypes other than CMC. Methods: We initially screened patients with CMC and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T (Treg) cells. After our initial case identifications, we explored 2 large cohorts of patients with wildtype forkhead box protein 3 and an immune dysregulation-polyendocrinopathy-enteropathy-X-linked (IPEX)-like phenotype for STAT1 mutations. Results: We identified 5 children with polyendocrinopathy, enteropathy, and dermatitis reminiscent of IPEX syndrome; all but 1 had a variety of mucosal and disseminated fungal infections. All patients lacked forkhead box protein 3 mutations but had uniallelic STAT1 mutations (c.629 G>T, p.R210I; c. 1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M [2 patients]). STAT1 phosphorylation in response to IFN-gamma, IL-6, and IL-21 was increased and prolonged. CD4(+) IL-17-producing T-cell numbers were diminished. All patients had normal Treg cell percentages in the CD4(+) T-cell compartment, and their function was intact in the 2 patients tested. Patients with cells available for study had normal levels of IL-2-induced STAT5 phosphorylation. Conclusions: Gain-of-function mutations in STAT1 can cause an IPEX-like phenotype with normal frequency and function of Treg cells. | - |
dc.language | 영어 | - |
dc.publisher | Mosby Inc. | - |
dc.title | Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.jaci.2012.11.054 | - |
dc.citation.journaltitle | Journal of Allergy and Clinical Immunology | - |
dc.identifier.wosid | 000320532800022 | - |
dc.identifier.scopusid | 2-s2.0-84878556463 | - |
dc.citation.endpage | 1623 | - |
dc.citation.number | 6 | - |
dc.citation.startpage | 1611 | - |
dc.citation.volume | 131 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Yim, Jae Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | REGULATORY T-CELLS | - |
dc.subject.keywordPlus | CHRONIC MUCOCUTANEOUS CANDIDIASIS | - |
dc.subject.keywordPlus | IPEX | - |
dc.subject.keywordPlus | DEFICIENCY | - |
dc.subject.keywordPlus | IMMUNODEFICIENCY | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | DISEASES | - |
dc.subject.keywordAuthor | Signal transducer and activator of transcription 1 | - |
dc.subject.keywordAuthor | immune dysregulation-polyendocrinopathy-enteropathy-X-linked | - |
dc.subject.keywordAuthor | forkhead box protein 3 | - |
dc.subject.keywordAuthor | regulatory T cell | - |
dc.subject.keywordAuthor | chronic mucocutaneous candidiasis | - |
dc.subject.keywordAuthor | aneurysms | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.