Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome

Mario Heindl; Norman Hndel; Joanne Ngeow; Janina Kionke; Christian Wittekind; Manja Kamprad; Anne Rensing-Ehl; Stephan Ehl; Julia Reifenberger; Christoph Loddenkemper; Jochen Maul; Albrecht Hoffmeister; Stefan Aretz; Wieland Kiess; Charis Eng; Holm H. Uhlig

doi:10.1053/j.gastro.2012.01.011

Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome

Mario Heindl, Norman Hndel, Joanne Ngeow, Janina Kionke, Christian Wittekind, Manja Kamprad, Anne Rensing-Ehl, Stephan Ehl, Julia Reifenberger, Christoph Loddenkemper, Jochen Maul, Albrecht Hoffmeister, Stefan Aretz, Wieland Kiess, Charis Eng, Holm H. Uhlig^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

67 Citations (Scopus)

Abstract

The Phosphatase And Tensin Homolog Deleted On Chromosome 10 (PTEN) regulates the phosphoinositol-3-kinase (PI3K)-AKT signaling pathway. In a series of 34 patients with PTEN mutations, we described gastrointestinal lymphoid hyperplasia, extensive hyperplastic tonsils, thymus hyperplasia, autoimmune lymphocytic thyroiditis, autoimmune hemolytic anemia, and colitis. Functional analysis of the gastrointestinal mucosa-associated lymphoid tissue revealed increased signaling via the PI3K-AKT pathway, including phosphorylation of S6 and increased cell proliferation, but also reduced apoptosis of CD20 ⁺CD10⁺ B cells. Reduced activity of PTEN therefore affects homeostasis of human germinal center B cells by increasing PI3K-AKT signaling via mammalian target of rapamycin as well as antiapoptotic signals.

Original language	English
Pages (from-to)	1093-1096.e6
Journal	Gastroenterology
Volume	142
Issue number	5
DOIs	https://doi.org/10.1053/j.gastro.2012.01.011
Publication status	Published - May 2012
Externally published	Yes

ASJC Scopus Subject Areas

Hepatology
Gastroenterology

Keywords

Bannayan Riley Ruvalcaba Syndrome
Cowden Syndrome
Hamartoma Tumor Syndrome

Access to Document

10.1053/j.gastro.2012.01.011

Cite this

Heindl, M., Hndel, N., Ngeow, J., Kionke, J., Wittekind, C., Kamprad, M., Rensing-Ehl, A., Ehl, S., Reifenberger, J., Loddenkemper, C., Maul, J., Hoffmeister, A., Aretz, S., Kiess, W., Eng, C., & Uhlig, H. H. (2012). Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome. Gastroenterology, 142(5), 1093-1096.e6. https://doi.org/10.1053/j.gastro.2012.01.011

@article{bd96d699a6454a428c22594c30cbb284,

title = "Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome",

abstract = "The Phosphatase And Tensin Homolog Deleted On Chromosome 10 (PTEN) regulates the phosphoinositol-3-kinase (PI3K)-AKT signaling pathway. In a series of 34 patients with PTEN mutations, we described gastrointestinal lymphoid hyperplasia, extensive hyperplastic tonsils, thymus hyperplasia, autoimmune lymphocytic thyroiditis, autoimmune hemolytic anemia, and colitis. Functional analysis of the gastrointestinal mucosa-associated lymphoid tissue revealed increased signaling via the PI3K-AKT pathway, including phosphorylation of S6 and increased cell proliferation, but also reduced apoptosis of CD20 +CD10+ B cells. Reduced activity of PTEN therefore affects homeostasis of human germinal center B cells by increasing PI3K-AKT signaling via mammalian target of rapamycin as well as antiapoptotic signals.",

keywords = "Bannayan Riley Ruvalcaba Syndrome, Cowden Syndrome, Hamartoma Tumor Syndrome",

author = "Mario Heindl and Norman Hndel and Joanne Ngeow and Janina Kionke and Christian Wittekind and Manja Kamprad and Anne Rensing-Ehl and Stephan Ehl and Julia Reifenberger and Christoph Loddenkemper and Jochen Maul and Albrecht Hoffmeister and Stefan Aretz and Wieland Kiess and Charis Eng and Uhlig, {Holm H.}",

year = "2012",

month = may,

doi = "10.1053/j.gastro.2012.01.011",

language = "English",

volume = "142",

pages = "1093--1096.e6",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "5",

}

Heindl, M, Hndel, N, Ngeow, J, Kionke, J, Wittekind, C, Kamprad, M, Rensing-Ehl, A, Ehl, S, Reifenberger, J, Loddenkemper, C, Maul, J, Hoffmeister, A, Aretz, S, Kiess, W, Eng, C & Uhlig, HH 2012, 'Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome', Gastroenterology, vol. 142, no. 5, pp. 1093-1096.e6. https://doi.org/10.1053/j.gastro.2012.01.011

TY - JOUR

T1 - Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome

AU - Heindl, Mario

AU - Hndel, Norman

AU - Ngeow, Joanne

AU - Kionke, Janina

AU - Wittekind, Christian

AU - Kamprad, Manja

AU - Rensing-Ehl, Anne

AU - Ehl, Stephan

AU - Reifenberger, Julia

AU - Loddenkemper, Christoph

AU - Maul, Jochen

AU - Hoffmeister, Albrecht

AU - Aretz, Stefan

AU - Kiess, Wieland

AU - Eng, Charis

AU - Uhlig, Holm H.

PY - 2012/5

Y1 - 2012/5

N2 - The Phosphatase And Tensin Homolog Deleted On Chromosome 10 (PTEN) regulates the phosphoinositol-3-kinase (PI3K)-AKT signaling pathway. In a series of 34 patients with PTEN mutations, we described gastrointestinal lymphoid hyperplasia, extensive hyperplastic tonsils, thymus hyperplasia, autoimmune lymphocytic thyroiditis, autoimmune hemolytic anemia, and colitis. Functional analysis of the gastrointestinal mucosa-associated lymphoid tissue revealed increased signaling via the PI3K-AKT pathway, including phosphorylation of S6 and increased cell proliferation, but also reduced apoptosis of CD20 +CD10+ B cells. Reduced activity of PTEN therefore affects homeostasis of human germinal center B cells by increasing PI3K-AKT signaling via mammalian target of rapamycin as well as antiapoptotic signals.

AB - The Phosphatase And Tensin Homolog Deleted On Chromosome 10 (PTEN) regulates the phosphoinositol-3-kinase (PI3K)-AKT signaling pathway. In a series of 34 patients with PTEN mutations, we described gastrointestinal lymphoid hyperplasia, extensive hyperplastic tonsils, thymus hyperplasia, autoimmune lymphocytic thyroiditis, autoimmune hemolytic anemia, and colitis. Functional analysis of the gastrointestinal mucosa-associated lymphoid tissue revealed increased signaling via the PI3K-AKT pathway, including phosphorylation of S6 and increased cell proliferation, but also reduced apoptosis of CD20 +CD10+ B cells. Reduced activity of PTEN therefore affects homeostasis of human germinal center B cells by increasing PI3K-AKT signaling via mammalian target of rapamycin as well as antiapoptotic signals.

KW - Bannayan Riley Ruvalcaba Syndrome

KW - Cowden Syndrome

KW - Hamartoma Tumor Syndrome

UR - http://www.scopus.com/inward/record.url?scp=84860176032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860176032&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2012.01.011

DO - 10.1053/j.gastro.2012.01.011

M3 - Article

AN - SCOPUS:84860176032

SN - 0016-5085

VL - 142

SP - 1093-1096.e6

JO - Gastroenterology

JF - Gastroenterology

IS - 5

ER -

Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome

Abstract

ASJC Scopus Subject Areas

Keywords

Access to Document

Other files and links

Fingerprint

Cite this