dc.contributor.author | Woellner, Cristina | |
dc.contributor.author | Gertz, E. Michael | |
dc.contributor.author | Schaeffer, Alejandro A. | |
dc.contributor.author | Lagos, Macarena | |
dc.contributor.author | Perro, Mario | |
dc.contributor.author | Glocker, Erik-Oliver | |
dc.contributor.author | Pietrogrande, Maria C. | |
dc.contributor.author | Cossu, Fausto | |
dc.contributor.author | Franco, Josee L. | |
dc.contributor.author | Matamoros, Nuria | |
dc.contributor.author | Pietrucha, Barbara | |
dc.contributor.author | Heropolitanska-Pliszka, Edyta | |
dc.contributor.author | Yeganeh, Mehdi | |
dc.contributor.author | Moin, Mostafa | |
dc.contributor.author | Espanol, Teresa | |
dc.contributor.author | Ehl, Stephan | |
dc.contributor.author | Gennery, Andrew R. | |
dc.contributor.author | Abinun, Mario | |
dc.contributor.author | Breborowicz, Anna | |
dc.contributor.author | Niehues, Tim | |
dc.contributor.author | Kilic, Sara Sebnem | |
dc.contributor.author | Junker, Anne | |
dc.contributor.author | Turvey, Stuart E. | |
dc.contributor.author | Plebani, Alessandro | |
dc.contributor.author | Sanchez, Berta | |
dc.contributor.author | Garty, Ben-Zion | |
dc.contributor.author | Pignata, Claudio | |
dc.contributor.author | Cancrini, Caterina | |
dc.contributor.author | Litzman, Jiri | |
dc.contributor.author | Sanal, Oezden | |
dc.contributor.author | Baumann, Ulrich | |
dc.contributor.author | Bacchetta, Rosa | |
dc.contributor.author | Hsu, Amy P. | |
dc.contributor.author | Davis, Joie N. | |
dc.contributor.author | Hammarstroem, Lennart | |
dc.contributor.author | Davies, E. Graham | |
dc.contributor.author | Eren, Efrem | |
dc.contributor.author | Arkwright, Peter D. | |
dc.contributor.author | Moilanen, Jukka S. | |
dc.contributor.author | Viemann, Dorothee | |
dc.contributor.author | Khan, Sujoy | |
dc.contributor.author | Laszlo Marodi | |
dc.contributor.author | Cant, Andrew J. | |
dc.contributor.author | Freeman, Alexandra F. | |
dc.contributor.author | Puck, Jennifer M. | |
dc.contributor.author | Holland, Steven M. | |
dc.contributor.author | Grimbacher, Bodo | |
dc.date.accessioned | 2019-12-10T10:41:39Z | |
dc.date.available | 2019-12-10T10:41:39Z | |
dc.date.issued | 2010 | |
dc.identifier.issn | 0091-6749 | |
dc.identifier.uri | https://doi.org/10.1016/j.jaci.2009.10.059 | |
dc.identifier.uri | http://hdl.handle.net/11655/14191 | |
dc.description.abstract | Background: The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and bony tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT-3) and severe reductions of T(H)17 cells. Objective: To determine whether there is a correlation between the genotype and the phenotype of patients with HIES and to establish diagnostic criteria to distinguish between STAT3 mutated and STAT3 wild-type patients. Methods: We collected clinical data, determined T(H)17 cell numbers, and sequenced STAT3 in 100 patients with a strong clinical suspicion of HIES and serum IgE > 1000 IU/mL. We explored diagnostic criteria by using a machine-learning approach to identify which features best predict a STAT3 mutation. Results: In 64 patients, we identified 31 different STAT3 mutations, 18 of which were novel. These included mutations at splice sites and outside the previously implicated DNA-binding and Src homology 2 domains. A combination of 5 clinical features predicted STAT3 mutations with 85% accuracy. T(H)17 cells were profoundly reduced in patients harboring STAT-3 mutations, whereas 10 of 13 patients without mutations had low (<1%) T(H)17 cells but were distinct by markedly reduced IFN-gamma-producing CD4(+)T cells. Conclusion: We propose the folio-wing diagnostic guidelines for STAT3-deficient HIES. Possible: IgE >1000IU/mL plus a weighted score of clinical features >30 based on recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high palate. Probable: These characteristics plus lack of T(H)17 cells or a family history for definitive HIES. Definitive: These characteristics plus a dominant-negative heterozygous mutation in STAT3. (J Allergy Clin Immunol 2010;125:424-32.) | |
dc.language.iso | en | |
dc.publisher | Mosby-Elsevier | |
dc.relation.isversionof | 10.1016/j.jaci.2009.10.059 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Allergy | |
dc.subject | Immunology | |
dc.title | Mutations In Stat3 And Diagnostic Guidelines For Hyper-Ige Syndrome | |
dc.type | info:eu-repo/semantics/article | |
dc.relation.journal | Journal Of Allergy And Clinical Immunology | |
dc.contributor.department | Çocuk Sağlığı ve Hastalıkları | |
dc.identifier.volume | 125 | |
dc.identifier.issue | 2 | |
dc.identifier.startpage | 424 | |
dc.identifier.endpage | 432 | |
dc.description.index | WoS | |