Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections

Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections

Copyright © 2017. Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 176(2017) vom: 30. März, Seite 77-86
1. Verfasser: Wentink, Marjolein (VerfasserIn)
Weitere Verfasser: Dalm, Virgil, Lankester, Arjan C, van Schouwenburg, Pauline A, Schölvinck, Liesbeth, Kalina, Tomas, Zachova, Radana, Sediva, Anna, Lambeck, Annechien, Pico-Knijnenburg, Ingrid, van Dongen, Jacques J M, Pac, Malgorzata, Bernatowska, Ewa, van Hagen, Martin, Driessen, Gertjan, van der Burg, Mirjam
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article APDS Apoptosis B cells B-cell differentiation PI3Kδ PIK3R1 protein, human EC 2.7.1.- Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137 mehr... Class Ia Phosphatidylinositol 3-Kinase PIK3CD protein, human Proto-Oncogene Proteins c-akt EC 2.7.11.1
Beschreibung
Zusammenfassung:Copyright © 2017. Published by Elsevier Inc.
BACKGROUND: Mutations in PIK3CD and PIK3R1 cause activated PI3K-δ 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
Beschreibung:Date Completed 05.06.2017
Date Revised 09.12.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2017.01.004