Browsing by Author "Matamoros, Núria"

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    Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome
    (Mosby-Elsevier, 2010-02) Woellner, Cristina; Gertz, Edward Michael; Schaffer, Alejandro A.; Lagos, Macarena; Perro, Mario; Glocker, Erik Oliver; Pietrogrande, Maria Cristina; Cossu, Fausto; Franko, Josè Luis; Matamoros, Núria; Pietrucha, Barbara Maria; Heropolitańska-Pliszka, Edyta; Yeganeh, Mehdi; Moin, Mostafa; Español, Theresa; Ehl, Stephan; Gennery, Andrew R.; Abinun, Mario A.; Brȩborowicz, Anna; Niehues, Tim; Junker, Anne K.; Turvey, Stuart E.; Plebani, Alessandro; Sánchez, Berta; Garty, Ben Zion; Pignata, Claudio; Cancrini, Caterina; Litzman, Jiří; Sanal, Özden; Baumann, Ulrich; Bacchetta, Rosa; Hsu, Amy P.; Davis, Joie N.; Hammarström, Lennart L.G.; Davis, Edward Graham; Eren, Efrem; Arkwright, Peter D.; Moilanen, Jukka S.; Viemann, Dorothee; Khan, Sujoy; Máródi, László D.R.; Cant, Andrew James; Freeman, Alexandra F.; Puck, Jennifer M.; Holland, Steven M.; Grimbacher, Bodo; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200
    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.