Autoimmunity, Intestinal Lymphoid Hyperplasia, and Defects in Mucosal B-Cell Homeostasis in Patients With PTEN Hamartoma Tumor Syndrome
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 l...
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| Veröffentlicht in: | Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2012-05, Vol.142 (5), p.1093-1096.e6 |
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| container_end_page | 1096.e6 |
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| container_issue | 5 |
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| container_title | Gastroenterology (New York, N.Y. 1943) |
| container_volume | 142 |
| creator | Heindl, Mario Händel, Norman Ngeow, Joanne Kionke, Janina Wittekind, Christian Kamprad, Manja Rensing–Ehl, Anne Ehl, Stephan Reifenberger, Julia Loddenkemper, Christoph Maul, Jochen Hoffmeister, Albrecht Aretz, Stefan Kiess, Wieland Eng, Charis Uhlig, Holm H |
| description | 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. |
| doi_str_mv | 10.1053/j.gastro.2012.01.011 |
| format | Article |
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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.</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1053/j.gastro.2012.01.011</identifier><identifier>PMID: 22266152</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Autoimmune Diseases - etiology ; B-Lymphocytes - immunology ; Bannayan Riley Ruvalcaba Syndrome ; Castleman Disease - etiology ; Child ; Child, Preschool ; Cowden Syndrome ; Female ; Gastroenterology and Hepatology ; Hamartoma Syndrome, Multiple - genetics ; Hamartoma Syndrome, Multiple - immunology ; Hamartoma Tumor Syndrome ; Homeostasis ; Humans ; Intestinal Diseases - etiology ; Male ; Middle Aged ; Mutation ; Phosphatidylinositol 3-Kinases - physiology ; Proto-Oncogene Proteins c-akt - physiology ; PTEN Phosphohydrolase - genetics ; Signal Transduction</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 2012-05, Vol.142 (5), p.1093-1096.e6</ispartof><rights>AGA Institute</rights><rights>2012 AGA Institute</rights><rights>Copyright © 2012 AGA Institute. 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| identifier | ISSN: 0016-5085 |
| ispartof | Gastroenterology (New York, N.Y. 1943), 2012-05, Vol.142 (5), p.1093-1096.e6 |
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| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier); Alma/SFX Local Collection |
| subjects | Adolescent Adult Autoimmune Diseases - etiology B-Lymphocytes - immunology Bannayan Riley Ruvalcaba Syndrome Castleman Disease - etiology Child Child, Preschool Cowden Syndrome Female Gastroenterology and Hepatology Hamartoma Syndrome, Multiple - genetics Hamartoma Syndrome, Multiple - immunology Hamartoma Tumor Syndrome Homeostasis Humans Intestinal Diseases - etiology Male Middle Aged Mutation Phosphatidylinositol 3-Kinases - physiology Proto-Oncogene Proteins c-akt - physiology PTEN Phosphohydrolase - genetics Signal Transduction |
| title | Autoimmunity, Intestinal Lymphoid Hyperplasia, and Defects in Mucosal B-Cell Homeostasis in Patients With PTEN Hamartoma Tumor Syndrome |
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