Genetic defects in PI3K delta affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373646" target="_blank" >RIV/00216208:11130/17:10373646 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/17:10373646
Result on the web
<a href="https://doi.org/10.1016/j.clim.2017.01.004" target="_blank" >https://doi.org/10.1016/j.clim.2017.01.004</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.clim.2017.01.004" target="_blank" >10.1016/j.clim.2017.01.004</a>

Result language
angličtina
Original language name
Genetic defects in PI3K delta affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections
Original language description
Background: Mutations in PIK3CD and PIK3R1 cause activated PI3K-8 syndrome (APDS) by dysregulation of the PI3K-AKT pathway. Methods: We studied precursor and peripheral B-cell differentiation and apoptosis via flowcytometry. Furthermore, we performed AKT-phosphorylation assays and somatic hypermutations (SHM) and class switch recombination (CSR) analysis. Results: We identified 13 patients of whom 3 had new mutations in PIK3CD or PIK3R1. Patients had low total B cell numbers with increased frequencies of transitional B cells and plasmablasts, while the precursor B-cell compartment in bone marrow was relatively normal. Basal AKT phosphorylation was increased in lymphocytes from APDS patients and natural effector B cells where most affected. PI3K mutations resulted in altered SHM and CSR and increased apoptosis. Conclusions: The B-cell compartment in APDS patients is affected by the mutations in PI3K. There is reduced differentiation beyond the transitional stage, increased AKT phosphorylation and increased apoptosis. This B cell phenotype contributes to the clinical phenotype. (C) 2017 Published by Elsevier Inc
Czech name
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Czech description
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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

Project
<a href="/en/project/NV15-28541A" target="_blank" >NV15-28541A: Dysregulation of immune system: characteristics of lymphocytes in patients with immunodeficiency and autoimmunity</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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