Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas.
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.
Ströbel
Philipp
P
Institute of Pathology, University of Wuerzburg, Germany. path036@mail.uni-wuerzburg.de
Helmreich
Markus
M
Menioudakis
Georgios
G
Lewin
Sharon R
SR
Rüdiger
Thomas
T
Bauer
Andrea
A
Hoffacker
Viola
V
Gold
Ralf
R
Nix
Wilfred
W
Schalke
Berthold
B
Elert
Olaf
O
Semik
Michael
M
Müller-Hermelink
Hans Konrad
HK
Marx
Alexander
A
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
D017493:Leukocyte Common Antigens