Clinical spectrum and features of activated phosphoinositide 3-kinase delta syndrome: A large patient cohort study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373863" target="_blank" >RIV/00216208:11130/17:10373863 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/17:10373863
Result on the web
<a href="https://doi.org/10.1016/j.jaci.2016.06.021" target="_blank" >https://doi.org/10.1016/j.jaci.2016.06.021</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jaci.2016.06.021" target="_blank" >10.1016/j.jaci.2016.06.021</a>
Alternative languages
Result language
angličtina
Original language name
Clinical spectrum and features of activated phosphoinositide 3-kinase delta syndrome: A large patient cohort study
Original language description
Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase delta (PI3K delta). Objective: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. Methods: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. Results: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3K delta in the central nervous system; consistent with this, PI3K delta is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. Conclusion: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3K delta inhibitors offer new prospects for APDS treatment.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Allergy and Clinical Immunology
ISSN
0091-6749
e-ISSN
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Volume of the periodical
139
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
597-606
UT code for WoS article
000397002400025
EID of the result in the Scopus database
2-s2.0-84996528817