Browsing by Author "Bruneau, Julie"

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    Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase delta syndrome 2: A cohort study
    (Mosby-Elsevier, 2016-07) Elkaim, Elodie; Neven, Benedicte; Bruneau, Julie; Mitsui-Sekinaka, Kanako; Stanislas, Aurelie; Heurtier, Lucie; Lucas, Carrie L.; Matthews, Helen; Deau, Marie-Celine; Sharapova, Svetlana; Curtis, James; Reichenbach, Janine; Glastre, Catherine; Parry, David A.; Arumugakani, Gururaj; McDermott, Elizabeth; Yamashita, Motoi; Moshous, Despina; Lamrini, Hicham; Otremba, Burkhard; Gennery, Andrew; Coulter, Tanya; Quinti, Isabella; Stephan, Jean-Louis; Lougaris, Vassilios; Brodszki, Nicholas; Barlogis, Vincent; Asano, Takaki; Galicier, Lionel; Boutboul, David; Nonoyama, Shigeaki; Cant, Andrew; Imai, Kohsuke; Picard, Capucine; Nejentsev, Sergey; Molina, Thierry Jo; Lenardo, Michael; Savic, Sinisa; Cavazzana, Marina; Fischer, Alain; Durandy, Anne; Kracker, Sven; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk İmmünoloji Bilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200
    Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) 2 (p110 delta-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]-R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85 alpha, p55 alpha, and p50 alpha) of class IA phosphoinositide 3-kinases. Objectives: We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort. Methods: The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed. Results: Mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract infections (100%), pneumonitis (71%), and chronic lymphoproliferation (89%, including adenopathy [75%], splenomegaly [43%], and upper respiratory tract lymphoid hyperplasia [48%]) were the most common features. Growth retardation was frequently noticed (45%). Other complications were mild neurodevelopmental delay (31%); malignant diseases (28%), most of them being B-cell lymphomas; autoimmunity (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell lymphopenia (88%) associated with an increased frequency of transitional B cells (93%), and decreased numbers of naive CD4 and naive CD8 cells but increased numbers of CD8 effector/memory T cells were predominant immunologic features. The majority of patients (89%) received immunoglobulin replacement; 3 patients were treated with rituximab, and 6 were treated with rapamycin initiated after diagnosis of APDS2. Five patients died from APDS2-related complications. Conclusion: APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, such as severe bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase delta inhibitors are possible treatment options.