title: Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas.
abstract: Myasthenia gravis (MG) is the leading paraneoplastic manifestation of thymomas and is probably related to the capacity of thymomas to mature and export potentially autoreactive T cells. Why some thymomas are MG associated (MG+) and others are not (MG-) has been unclear. We addressed this question by comparing the percentages of intratumorous naive mature CD45RA+ thymocytes in 9 MG(+) and in 13 MG(-) thymomas by fluorescence-activated cell sorting analysis. Our results show that intratumorous naive CD4 T cells were present in all MG(+) thymomas and in one MG(-) thymoma with the development of MG only 2 months after surgery. By contrast, the percentage of naive CD4(+) T cells was significantly reduced in all 13 MG(-) thymomas (P <.0001). Alterations in intratumorous thymopoiesis were reflected by corresponding alterations of naive T-cell subset composition in the blood, in that only MG(-) patients had significantly decreased levels (P =.02) of naive CD4(+) T cells compared with age- and sex-matched control persons. We conclude that paraneoplastic MG is highly associated with the efficiency of thymomas to produce and export naive CD4(+) T cells. The acquisition of the CD45RA(+) phenotype on CD4(+) T cells during terminal intratumorous thymopoiesis is associated with the presence of MG in most thymoma patients.
authors.affiliation: Institute of Pathology, University of Wuerzburg, Germany. path036@mail.uni-wuerzburg.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Markus
authors.initials: M
authors.lastname: Helmreich
authors.forename: Georgios
authors.initials: G
authors.lastname: Menioudakis
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Thomas
authors.initials: T
authors.lastname: Rüdiger
authors.forename: Andrea
authors.initials: A
authors.lastname: Bauer
authors.forename: Viola
authors.initials: V
authors.lastname: Hoffacker
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Wilfred
authors.initials: W
authors.lastname: Nix
authors.forename: Berthold
authors.initials: B
authors.lastname: Schalke
authors.forename: Olaf
authors.initials: O
authors.lastname: Elert
authors.forename: Michael
authors.initials: M
authors.lastname: Semik
authors.forename: Hans Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
mesh_terms: D000328:Adult; D000368:Aged; D001773:Blood Cells; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000276:immunology / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013945:Thymoma / Q000150:complications / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
chemical_list: D017493:Leukocyte Common Antigens