Autosomal Dominant STAT3 Deficiency and Hyper-IgE Syndrome: Molecular, Cellular, and Clinical Features From a French National Survey.

Marie-Olivia Chandesris 1, 2, 3 Isabelle Melki 3 Angels Natividad 3 Anne Puel 3 Claire Fieschi 4, 5 Ling Yun 3 Caroline Thumerelle 6 Eric Oksenhendler 5 David Boutboul 4 Caroline Thomas 7 Cyrille Hoarau 8 Yvon Lebranchu 8 Jean-Louis Stephan 9 Celine Cazorla 10 Nathalie Aladjidi 11 Marguerite Micheau 11 François Tron 12 André Baruchel 13 Vincent Barlogis 14 Gilles Palenzuela 15 Catherine Mathey 16 Stéphane Dominique 17 Gérard Body 18 Martine Munzer 19 Fanny Fouyssac 20 Rolland Jaussaud 21 Brigitte Bader-Meunier 22 Nizar Mahlaoui 2, 22 Stéphane Blanche 22 Marianne Debré 22 Muriel Le Bourgeois 23 Virginie Gandemer 24 Nathalie Lambert 25 Virginie Grandin 25 Stéphanie Ndaga 25 Corinne Jacques 25 Chantal Harre 25 Monique Forveille 25 Marie-Alexandra Alyanakian 22 Anne Durandy 2, 26 Christine Bodemer 27 Felipe Suarez 1, 2 Olivier Hermine 2, 1 Olivier Lortholary 2, 28 Jean-Laurent Casanova 3, 22, 29 Alain Fischer 2, 22, 26 Capucine Picard 2, 3, 22, 25, *
* Auteur correspondant
1 ERL 8254 - Laboratoire d'hématologie
IMAGINE - U1163 - Imagine - Institut des maladies génétiques : ERL8254
Abstract : ABSTRACT: Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3. Low levels of interleukin (IL)-6-dependent phosphorylation and nuclear translocation (or accumulation) of STAT3 were observed in Epstein-Barr virus-transformed B lymphocytes (EBV-B cells) from all STAT3-deficient patients tested. The immunologic phenotype was characterized by high serum IgE levels (96% of the patients), memory B-cell lymphopenia (94.5%), and hypereosinophilia (80%). A low proportion of IL-17A-producing circulating T cells was found in 14 of the 15 patients tested. Mucocutaneous infections were the most frequent, typically caused by Staphylococcus aureus (all patients) and Candida albicans (85%). Up to 90% of the patients had pneumonia, mostly caused by Staph. aureus (31%) or Streptococcus pneumoniae (30%). Recurrent pneumonia was associated with secondary bronchiectasis and pneumatocele (67%), as well as secondary aspergillosis (22%). Up to 92% of the patients had dermatitis and connective tissue abnormalities, with facial dysmorphism (95%), retention of decidual teeth (65%), osteopenia (50%), and hyperextensibility (50%). Four patients developed non-Hodgkin lymphoma. The clinical outcome was favorable, with 56 patients, including 43 adults, still alive at the end of study (mean age, 21 yr; range, 1 mo to 46 yr). Only 4 patients died, 3 from severe bacterial infection (aged 1, 15, and 29 yr, respectively). Antibiotic prophylaxis (90% of patients), antifungal prophylaxis (50%), and IgG infusions (53%) improved patient health, as demonstrated by the large decrease in pneumonia recurrence. Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented.
Type de document :
Article dans une revue
Medicine, Lippincott, Williams & Wilkins, 2012, 91 (4), pp.e1-e19. 〈10.1097/MD.0b013e31825f95b9〉
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Contributeur : Hervé De Villemeur <>
Soumis le : mercredi 11 juillet 2012 - 18:14:38
Dernière modification le : mercredi 29 août 2018 - 01:10:32

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Marie-Olivia Chandesris, Isabelle Melki, Angels Natividad, Anne Puel, Claire Fieschi, et al.. Autosomal Dominant STAT3 Deficiency and Hyper-IgE Syndrome: Molecular, Cellular, and Clinical Features From a French National Survey.. Medicine, Lippincott, Williams & Wilkins, 2012, 91 (4), pp.e1-e19. 〈10.1097/MD.0b013e31825f95b9〉. 〈inserm-00717018〉

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