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Title: | Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase delta syndrome 2: A cohort study |
Authors: | 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 Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk İmmünoloji Bilim Dalı. 0000-0001-8571-2581 Kılıç, Sara Şebnem AAH-1658-2021 34975059200 |
Keywords: | Allergy Immunology Primary immunodeficiency Phosphoinositide 3-kinase Activated phosphoinositide 3-kinase delta syndrome P110 delta-activating mutations causing senescent T cells Lymphadenopathy And immunodeficiency Hyper-IgM Adenopathy Immunodeficiency Antibody deficiency P85 alpha P110 delta Human immunodeficiency Mutations Kinase Cells |
Issue Date: | Jul-2016 |
Publisher: | Mosby-Elsevier |
Citation: | Elkaim, E. vd. (2016). "Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase delta syndrome 2: A cohort study". Journal of Allergy and Clinical Immunology, 138(1), 210-218. |
Abstract: | 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. |
URI: | https://doi.org/10.1016/j.jaci.2016.03.022 https://www.sciencedirect.com/science/article/pii/S0091674916300975 http://hdl.handle.net/11452/29255 |
ISSN: | 0091-6749 1097-6825 |
Appears in Collections: | Scopus Web of Science |
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