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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00064203:_____/17:10373646

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/NV15-28541A" target="_blank" >NV15-28541A: Dysregulace imunitního systému: vlastnosti lymfocytů u pacientů s immunodeficiencí a autoimunitními projevy</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical Immunology

ISSN

1521-6616

e-ISSN

—

Svazek periodika

176

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

77-86

Kód UT WoS článku

000396965200010

EID výsledku v databázi Scopus

2-s2.0-85010219845