Academic Journal
Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome
| العنوان: | Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome |
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| المؤلفون: | C. Woellner, E. M. Gertz, A. A. Schäffer, M. Lagos, M. Perro, E. O. Glocker, F. Cossu, J. L. Franco, N. Matamoros, B. Pietrucha, E. Heropolitanska Pliszka, M. Yeganeh, M. Moin, T. Español, S. Ehl, A. R. Gennery, M. Abinun, A. Breborowicz, T. Niehues, S. Sebnem Kilic, A. Junker, S. E. Turvey, A. Plebani, B. Sánchez, B. Z. Garty, C. Pignata, C. Cancrini, J. Litzman, Ö. Sanal, U. Baumann, R. Bacchetta, A. P. Hsu, J. N. Davis, L. Hammarström, E. G. Davies, E. Eren, P. D. Arkwright, J. S. Moilanen, D. Viemann, S. Khan, L. Maródi, A. J. Cant, A. F. Freeman, J. M. Puck, S. M. Holland, B. Grimbacher, M.C. Pietrogrande |
| المساهمون: | C. Woellner, E.M. Gertz, A.A. Schäffer, M. Lago, M. Perro, E.O. Glocker, M.C. Pietrogrande, F. Cossu, J.L. Franco, N. Matamoro, B. Pietrucha, E. Heropolitanska Pliszka, M. Yeganeh, M. Moin, T. Español, S. Ehl, A.R. Gennery, M. Abinun, A. Breborowicz, T. Niehue, S. Sebnem Kilic, A. Junker, S.E. Turvey, A. Plebani, B. Sánchez, B.Z. Garty, C. Pignata, C. Cancrini, J. Litzman, Ö. Sanal, U. Baumann, R. Bacchetta, A.P. Hsu, J.N. Davi, L. Hammarström, E.G. Davie, E. Eren, P.D. Arkwright, J.S. Moilanen, D. Viemann, S. Khan, L. Maródi, A.J. Cant, A.F. Freeman, J.M. Puck, S.M. Holland, B. Grimbacher |
| بيانات النشر: | Mosby |
| سنة النشر: | 2010 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Hyper-IgE syndrome, HIES, Job syndrome, TH17 cells, STAT3 mutations, diagnostic guidelines, Settore MED/38 - Pediatria Generale e Specialistica, Settore MED/03 - Genetica Medica |
| الوصف: | 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 dominantnegative mutations in the signal transducer and activator of transcription 3 (STAT3) and severe reductions of TH17 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 TH17 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. TH17 cells were profoundly reduced in patients harboring STAT3 mutations, whereas 10 of 13 patients without mutations had low (<1%) TH17 cells but were distinct by markedly reduced IFN-g–producing CD41T cells. Conclusion: We propose the following 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 TH17 cells or a family history for definitive HIES. Definitive: These characteristics plus a dominant-negative heterozygous mutation in STAT3 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/20159255; info:eu-repo/semantics/altIdentifier/wos/WOS:000274764000022; volume:125; issue:2; firstpage:424; lastpage:432; journal:JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY; http://hdl.handle.net/2434/156073; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-76049116822 |
| DOI: | 10.1016/j.jaci.2009.10.059 |
| الاتاحة: | http://hdl.handle.net/2434/156073 https://doi.org/10.1016/j.jaci.2009.10.059 |
| رقم الانضمام: | edsbas.E52D6108 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jaci.2009.10.059 |
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