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
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245 1 0 |a Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections 
264 1 |c 2017 
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500 |a Date Revised 09.12.2020 
500 |a published: Print-Electronic 
500 |a Citation Status MEDLINE 
520 |a Copyright © 2017. Published by Elsevier Inc. 
520 |a BACKGROUND: Mutations in PIK3CD and PIK3R1 cause activated PI3K-δ syndrome (APDS) by dysregulation of the PI3K-AKT pathway 
520 |a 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 
520 |a 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 
520 |a 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 
650 4 |a Journal Article 
650 4 |a APDS 
650 4 |a Apoptosis 
650 4 |a B cells 
650 4 |a B-cell differentiation 
650 4 |a PI3Kδ 
650 7 |a PIK3R1 protein, human  |2 NLM 
650 7 |a EC 2.7.1.-  |2 NLM 
650 7 |a Class I Phosphatidylinositol 3-Kinases  |2 NLM 
650 7 |a EC 2.7.1.137  |2 NLM 
650 7 |a Class Ia Phosphatidylinositol 3-Kinase  |2 NLM 
650 7 |a EC 2.7.1.137  |2 NLM 
650 7 |a PIK3CD protein, human  |2 NLM 
650 7 |a EC 2.7.1.137  |2 NLM 
650 7 |a Proto-Oncogene Proteins c-akt  |2 NLM 
650 7 |a EC 2.7.11.1  |2 NLM 
700 1 |a Dalm, Virgil  |e verfasserin  |4 aut 
700 1 |a Lankester, Arjan C  |e verfasserin  |4 aut 
700 1 |a van Schouwenburg, Pauline A  |e verfasserin  |4 aut 
700 1 |a Schölvinck, Liesbeth  |e verfasserin  |4 aut 
700 1 |a Kalina, Tomas  |e verfasserin  |4 aut 
700 1 |a Zachova, Radana  |e verfasserin  |4 aut 
700 1 |a Sediva, Anna  |e verfasserin  |4 aut 
700 1 |a Lambeck, Annechien  |e verfasserin  |4 aut 
700 1 |a Pico-Knijnenburg, Ingrid  |e verfasserin  |4 aut 
700 1 |a van Dongen, Jacques J M  |e verfasserin  |4 aut 
700 1 |a Pac, Malgorzata  |e verfasserin  |4 aut 
700 1 |a Bernatowska, Ewa  |e verfasserin  |4 aut 
700 1 |a van Hagen, Martin  |e verfasserin  |4 aut 
700 1 |a Driessen, Gertjan  |e verfasserin  |4 aut 
700 1 |a van der Burg, Mirjam  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Clinical immunology (Orlando, Fla.)  |d 1999  |g 176(2017) vom: 30. März, Seite 77-86  |w (DE-627)NLM098196855  |x 1521-7035  |7 nnns 
773 1 8 |g volume:176  |g year:2017  |g day:30  |g month:03  |g pages:77-86 
856 4 0 |u http://dx.doi.org/10.1016/j.clim.2017.01.004  |3 Volltext 
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