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.
authors.affiliation: Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Heindl
authors.forename: Norman
authors.initials: N
authors.lastname: Händel
authors.forename: Joanne
authors.initials: J
authors.lastname: Ngeow
authors.forename: Janina
authors.initials: J
authors.lastname: Kionke
authors.forename: Christian
authors.initials: C
authors.lastname: Wittekind
authors.forename: Manja
authors.initials: M
authors.lastname: Kamprad
authors.forename: Anne
authors.initials: A
authors.lastname: Rensing-Ehl
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
authors.forename: Julia
authors.initials: J
authors.lastname: Reifenberger
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Jochen
authors.initials: J
authors.lastname: Maul
authors.forename: Albrecht
authors.initials: A
authors.lastname: Hoffmeister
authors.forename: Stefan
authors.initials: S
authors.lastname: Aretz
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Holm H
authors.initials: HH
authors.lastname: Uhlig
mesh_terms: D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000209:etiology*; D001402:B-Lymphocytes / Q000276:immunology*; D005871:Castleman Disease / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007410:Intestinal Diseases / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human