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Blood, 1 July 2002, Vol. 100, No. 1, pp. 159-166
IMMUNOBIOLOGY
Paraneoplastic myasthenia gravis correlates with generation of
mature naive CD4+ T cells in thymomas
Philipp Ströbel,
Markus Helmreich,
Georgios Menioudakis,
Sharon R. Lewin,
Thomas Rüdiger,
Andrea Bauer,
Viola Hoffacker,
Ralf Gold,
Wilfred Nix,
Berthold Schalke,
Olaf Elert,
Michael Semik,
Hans Konrad Müller-Hermelink, and
Alexander Marx
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.
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.
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