Autoimmunity, Intestinal Lymphoid Hyperplasia, and Defects in Mucosal B-Cell Homeostasis in Patients With PTEN Hamartoma Tumor Syndrome

被引：63

作者：

Heindl, Mario ^{[1
]}

Haendel, Norman ^{[1
]}

Ngeow, Joanne ^{[2
,3
]}

Kionke, Janina ^{[4
]}

Wittekind, Christian ^{[5
]}

Kamprad, Manja ^{[6
]}

Rensing-Ehl, Anne ^{[7
]}

Ehl, Stephan ^{[7
]}

Reifenberger, Julia ^{[8
]}

Loddenkemper, Christoph ^{[9
]}

Maul, Jochen ^{[10
]}

Hoffmeister, Albrecht ^{[11
]}

Aretz, Stefan ^{[4
]}

Kiess, Wieland ^{[1
]}

Eng, Charis ^{[2
,3
,12
,13
]}

Uhlig, Holm H. ^{[1
,14
]}

机构：

[1] Univ Leipzig, Hosp Children & Adolescents, Leipzig, Germany

[2] Cleveland Clin, Genom Med Inst, Lerner Res Inst, Taussig Canc Inst, Cleveland, OH 44106 USA

[3] Cleveland Clin, Stanley Shalom Zielony Inst Nursing Excellence, Cleveland, OH 44106 USA

[4] Univ Bonn, Inst Human Genet, Biomed Ctr, Bonn, Germany

[5] Univ Leipzig, Inst Pathol, Leipzig, Germany

[6] Univ Leipzig, Inst Immunol & Transfus Med, Leipzig, Germany

[7] Univ Med Ctr, Ctr Chron Immunodeficiency, Freiburg, Germany

[8] Univ Dusseldorf, Dept Dermatol, Dusseldorf, Germany

[9] Charite, Inst Pathol, Berlin, Germany

[10] Charite, Dept Med Gastroenterol Rheumatol Infect Dis 1, D-13353 Berlin, Germany

[11] Univ Leipzig, Dept Internal Med, Leipzig, Germany

[12] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA

[13] Case Western Reserve Univ, Sch Med, CASE Comprehens Canc Ctr, Cleveland, OH USA

[14] Univ Oxford, Translat Gastroenterol Unit, Oxford OX3 9DU, England

来源：

GASTROENTEROLOGY | 2012年 / 142卷 / 05期

关键词：

Bannayan Riley Ruvalcaba Syndrome; Cowden Syndrome; Hamartoma Tumor Syndrome; RILEY-RUVALCABA-SYNDROME; PROMOTER MUTATIONS; GERMLINE MUTATION; REFERENCE VALUES; DISEASE; PROTEIN; MICE;

D O I：

10.1053/j.gastro.2012.01.011

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：1093 / +

页数：10

共 27 条

[1] Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function
Anzelon, AN
Wu, H
Rickert, RC
[J]. NATURE IMMUNOLOGY, 2003, 4 (03) : 287 - 294
[2] Emergence of the PI3-kinase pathway as a central modulator of normal and aberrant B cell differentiation
Baracho, G. V.
Miletic, A. V.
Omori, S. A.
Cato, M. H.
Rickert, R. C.
[J]. CURRENT OPINION IN IMMUNOLOGY, 2011, 23 (02) : 178 - 183
[3] Bannayan-Riley-Ruvalcaba syndrome with reactive nodular lymphoid hyperplasia and autism and a PTEN mutation
Boccone, Loredana
Dessi, Valentina
Zappu, Antonietta
Piga, Silvia
Piludu, Maria Bonaria
Rais, Marco
Massidda, Carlo
De Virgiliis, Stefano
Cao, Antonio
Loudianos, Georgios
[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2006, 140A (18) : 1965 - 1969
[4] Suppression of Phosphatidylinositol 3,4,5-Trisphosphate Production Is a Key Determinant of B Cell Anergy
Browne, Cecille D.
Del Nagro, Christopher J.
Cato, Matthew H.
Dengler, Hart S.
Rickert, Robert C.
[J]. IMMUNITY, 2009, 31 (05) : 749 - 760
[5] BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten
Cheng, Shuhua
Hsia, Constance Yu
Feng, Biao
Liou, Mei-Ling
Fang, Xiaoying
Pandolfi, Pier Paolo
Liou, Hsiou-Chi
[J]. CELL RESEARCH, 2009, 19 (02) : 196 - 207
[6] Impaired Fas response and autoimmunity in Pten+/- mice
Di Cristofano, A
Kotsi, P
Peng, YF
Cordon-Cardo, C
Elkon, KB
Pandolfi, PP
[J]. SCIENCE, 1999, 285 (5436) : 2122 - 2125
[7] Cell-Cell-Neighborhood Relations in Tissue Sections-A Quantitative Model for Tissue Cytometry
Haendel, N.
Brockel, A.
Heindl, M.
Klein, E.
Uhlig, H. H.
[J]. CYTOMETRY PART A, 2009, 75A (04) : 356 - 361
[8] Frequent Gastrointestinal Polyps and Colorectal Adenocarcinomas in a Prospective Series of PTEN Mutation Carriers
Heald, Brandie
Mester, Jessica
Rybicki, Lisa
Orloff, Mohammed S.
Burke, Carol A.
Eng, Charis
[J]. GASTROENTEROLOGY, 2010, 139 (06) : 1927 - 1933
[9] Herklotz R, 2006, Ther Umsch, V63, P5, DOI 10.1024/0040-5930.63.1.5
[10] PTEN loss in the continuum of common cancers, rare syndromes and mouse models
Hollander, M. Christine
Blumenthal, Gideon M.
Dennis, Phillip A.
[J]. NATURE REVIEWS CANCER, 2011, 11 (04) : 289 - 301

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