Pathomechanisms of paraneoplastic myasthenia gravis.

Autor: Ströbel P; Institute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080, Wuerzburg, Germany. path036@mail.uni-wuerzburg.de, Preisshofen T, Helmreich M, Müller-Hermelink HK, Marx A
Jazyk: angličtina
Zdroj: Clinical & developmental immunology [Clin Dev Immunol] 2003 Mar; Vol. 10 (1), pp. 7-12.
DOI: 10.1080/10446670310001598528
Abstrakt: 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.
Databáze: MEDLINE