Pathomechanisms of Paraneoplastic Myasthenia Gravis
Thymic T cell development is characterized by sequential selection processes to ensure generation of a self-tolerant, immuncompetent mature T cell repertoire. Malfunction of any of these selection processes may potentially result in either immunodeficiency or autoimmunity. Myasthenia gravis (MG) is...
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| Format: | Article |
| Language: | English |
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Wiley
2003-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1080/10446670310001598528 |
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| author | Philipp Ströbel Tobias Preisshofen Markus Helmreich Hans Konrad Müller-Hermelink Alexander Marx |
| author_facet | Philipp Ströbel Tobias Preisshofen Markus Helmreich Hans Konrad Müller-Hermelink Alexander Marx |
| author_sort | Philipp Ströbel |
| collection | DOAJ |
| description | Thymic T cell development is characterized by sequential selection processes to ensure generation of a self-tolerant, immuncompetent mature T cell repertoire. Malfunction of any of these selection processes may potentially result in either immunodeficiency or autoimmunity. Myasthenia gravis (MG) is a typical autoimmune manifestation of thymic epithelial tumors (thymomas) and is related to the capacity of these tumors to generate and export mature T cells. Analysis of the factors that lead to autoimmunization in thymomas will help to understand the mechanisms that prevent MG under physiological conditions in humans. In a comparison of MG(+) and MG(-) thymomas, we could show that only thymomas capable of generating mature CD45RA+CD4+ T cells are associated with MG (p< 0.0001), while terminal thymopoiesis was abrogated in MG(-) thymomas. In particular, acquisition of the CD27+CD45RA+ phenotype appears to be a critical checkpoint of late T cell development in the human thymus and may play an important role in the prevention of autoimmunity. Moreover, MG(-) thymomas were virtually depleted of regulatory (CD4+CD25+) T cells (regT), while regT were readily detectable in MG(+) thymomas, albeit at significantly reduced numbers compared to control thymuses. Thus, in MG(+) thymoma patients, thymectomy apparently also results in removal of a regulatory T cell pool and may explain the frequent temporary postoperative deterioration of MG in these patients. |
| format | Article |
| id | doaj-art-e9828324ad0349e9b78e643cac131c44 |
| institution | OA Journals |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2003-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-e9828324ad0349e9b78e643cac131c442025-08-20T02:22:15ZengWileyClinical and Developmental Immunology1740-25221740-25302003-01-0110171210.1080/10446670310001598528Pathomechanisms of Paraneoplastic Myasthenia GravisPhilipp Ströbel0Tobias Preisshofen1Markus Helmreich2Hans Konrad Müller-Hermelink3Alexander Marx4Institute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg 97080, GermanyInstitute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg 97080, GermanyInstitute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg 97080, GermanyInstitute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg 97080, GermanyInstitute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg 97080, GermanyThymic T cell development is characterized by sequential selection processes to ensure generation of a self-tolerant, immuncompetent mature T cell repertoire. Malfunction of any of these selection processes may potentially result in either immunodeficiency or autoimmunity. Myasthenia gravis (MG) is a typical autoimmune manifestation of thymic epithelial tumors (thymomas) and is related to the capacity of these tumors to generate and export mature T cells. Analysis of the factors that lead to autoimmunization in thymomas will help to understand the mechanisms that prevent MG under physiological conditions in humans. In a comparison of MG(+) and MG(-) thymomas, we could show that only thymomas capable of generating mature CD45RA+CD4+ T cells are associated with MG (p< 0.0001), while terminal thymopoiesis was abrogated in MG(-) thymomas. In particular, acquisition of the CD27+CD45RA+ phenotype appears to be a critical checkpoint of late T cell development in the human thymus and may play an important role in the prevention of autoimmunity. Moreover, MG(-) thymomas were virtually depleted of regulatory (CD4+CD25+) T cells (regT), while regT were readily detectable in MG(+) thymomas, albeit at significantly reduced numbers compared to control thymuses. Thus, in MG(+) thymoma patients, thymectomy apparently also results in removal of a regulatory T cell pool and may explain the frequent temporary postoperative deterioration of MG in these patients.http://dx.doi.org/10.1080/10446670310001598528 |
| spellingShingle | Philipp Ströbel Tobias Preisshofen Markus Helmreich Hans Konrad Müller-Hermelink Alexander Marx Pathomechanisms of Paraneoplastic Myasthenia Gravis Clinical and Developmental Immunology |
| title | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
| title_full | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
| title_fullStr | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
| title_full_unstemmed | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
| title_short | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
| title_sort | pathomechanisms of paraneoplastic myasthenia gravis |
| url | http://dx.doi.org/10.1080/10446670310001598528 |
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