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Article Dans Une Revue Journal of Allergy and Clinical Immunology Année : 2016

Clinical and immunologic phenotype associated with activated ă phosphoinositide 3-kinase delta syndrome 2: A cohort study

Elodie Elkaim
  • Fonction : Auteur
Kanako Mitsui-Sekinaka
  • Fonction : Auteur
Aurelie Stanislas
  • Fonction : Auteur
Lucie Heurtier
  • Fonction : Auteur
Carrie L. Lucas
  • Fonction : Auteur
Marie-Celine Deau
  • Fonction : Auteur
Svetlana Sharapova
  • Fonction : Auteur
James Curtis
  • Fonction : Auteur
Catherine Glastre
  • Fonction : Auteur
David A. Parry
  • Fonction : Auteur
Gururaj Arumugakani
  • Fonction : Auteur
Elizabeth Mcdermott
  • Fonction : Auteur
Sara Sebnem Kilic
  • Fonction : Auteur
Motoi Yamashita
  • Fonction : Auteur
Hicham Lamrini
  • Fonction : Auteur
Burkhard Otremba
  • Fonction : Auteur
Tanya Coulter
  • Fonction : Auteur
Isabella Quinti
  • Fonction : Auteur
Vassilios Lougaris
  • Fonction : Auteur
Nicholas Brodszki
  • Fonction : Auteur
Takaki Asano
Shigeaki Nonoyama
  • Fonction : Auteur
Andrew Cant
  • Fonction : Auteur
Kohsuke Imai
  • Fonction : Auteur
Sergey Nejentsev
  • Fonction : Auteur
Sinisa Savic
  • Fonction : Auteur
Sven Kracker

Résumé

Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) 2 ă (p110 delta-activating mutations causing senescent T cells, ă lymphadenopathy, and immunodeficiency [PASLI]-R1), a recently ă described primary immunodeficiency, results from autosomal dominant ă mutations in PIK3R1, the gene encoding the regulatory subunit (p85 ă alpha, p55 alpha, and p50 alpha) of class IA phosphoinositide 3-kinases. ă Objectives: We sought to review the clinical, immunologic, and ă histopathologic phenotypes of APDS2 in a genetically defined ă international patient cohort. ă Methods: The medical and biological records of 36 patients with ă genetically diagnosed APDS2 were collected and reviewed. ă Results: Mutations within splice acceptor and donor sites of exon 11 of ă the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract ă infections (100%), pneumonitis (71%), and chronic lymphoproliferation ă (89%, including adenopathy [75%], splenomegaly [43%], and upper ă respiratory tract lymphoid hyperplasia [48%]) were the most common ă features. Growth retardation was frequently noticed (45%). Other ă complications were mild neurodevelopmental delay (31%); malignant ă diseases (28%), most of them being B-cell lymphomas; autoimmunity ă (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased ă serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell ă lymphopenia (88%) associated with an increased frequency of ă transitional B cells (93%), and decreased numbers of naive CD4 and ă naive CD8 cells but increased numbers of CD8 effector/memory T cells ă were predominant immunologic features. The majority of patients (89%) ă received immunoglobulin replacement; 3 patients were treated with ă rituximab, and 6 were treated with rapamycin initiated after diagnosis ă of APDS2. Five patients died from APDS2-related complications. ă Conclusion: APDS2 is a combined immunodeficiency with a variable ă clinical phenotype. Complications are frequent, such as severe bacterial ă and viral infections, lymphoproliferation, and lymphoma similar to ă APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, ă likely in the near future, selective phosphoinositide 3-kinase delta ă inhibitors are possible treatment options.

Dates et versions

hal-01482361 , version 1 (03-03-2017)

Identifiants

Citer

Elodie Elkaim, Bénédicte Neven, Julie Bruneau, Kanako Mitsui-Sekinaka, Aurelie Stanislas, et al.. Clinical and immunologic phenotype associated with activated ă phosphoinositide 3-kinase delta syndrome 2: A cohort study. Journal of Allergy and Clinical Immunology, 2016, 138 (1), pp.210+. ⟨10.1016/j.jaci.2016.03.022⟩. ⟨hal-01482361⟩
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