Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2 : A cohort study
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-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 (p85α, p55α, and p50α) 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 δ inhibitors are possible treatment options.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:138 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 138(2016), 1 vom: 24. Juli, Seite 210-218.e9 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 15.06.2017 Date Revised 29.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2016.03.022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM260704288 |
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| 100 | 1 | |a Elkaim, Elodie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2 |b A cohort study |
| 264 | 1 | |c 2016 | |
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| 500 | |a Date Completed 15.06.2017 | ||
| 500 | |a Date Revised 29.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-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 (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases | ||
| 520 | |a OBJECTIVES: We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort | ||
| 520 | |a METHODS: The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed | ||
| 520 | |a 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 | ||
| 520 | |a 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 δ inhibitors are possible treatment options | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Primary immunodeficiency | |
| 650 | 4 | |a activated phosphoinositide 3-kinase δ syndrome | |
| 650 | 4 | |a adenopathy | |
| 650 | 4 | |a and immunodeficiency | |
| 650 | 4 | |a antibody deficiency | |
| 650 | 4 | |a hyper-IgM | |
| 650 | 4 | |a immunodeficiency | |
| 650 | 4 | |a lymphadenopathy | |
| 650 | 4 | |a p110δ | |
| 650 | 4 | |a p110δ-activating mutations causing senescent T cells | |
| 650 | 4 | |a p85α | |
| 650 | 4 | |a phosphoinositide 3-kinase | |
| 650 | 7 | |a RNA Splice Sites |2 NLM | |
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