Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/29255
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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