Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4+ T cells in thymomas

Author:

Ströbel Philipp1,Helmreich Markus1,Menioudakis Georgios1,Lewin Sharon R.1,Rüdiger Thomas1,Bauer Andrea1,Hoffacker Viola1,Gold Ralf1,Nix Wilfred1,Schalke Berthold1,Elert Olaf1,Semik Michael1,Müller-Hermelink Hans Konrad1,Marx Alexander1

Affiliation:

1. From the Institute of Pathology, University of Wuerzburg; Department of Neurology, Universities of Wuerzburg, Mainz, and Regensburg; Department of Thoracic and Cardiac Surgery, Universities of Wuerzburg and Muenster, Germany; and Department of Microbiology and Immunology, University of Melbourne, Australia.

Abstract

AbstractMyasthenia 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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