CD45 isoform expression in autoimmune myasthenia gravis.
In myasthenia gravis (MG), humoral and cellular immune mechanisms are involved in the autoimmune pathogenesis. In this study, we investigated the role of the CD45 molecule in MG, having recently reported an association in multiple sclerosis. CD45, a protein-tyrosine phophatase receptor type C (PTPRC), is essential for both thymic selection and peripheral activation of T and B cells. Our aims were to determine (a) the prevalence of a functional mutation in the CD45 gene (exon 4 77C --> G; prevalence analysis), and (b) the distribution of memory (CD45RO+) and naive (CD45RA+) T cells in the peripheral blood (subset analysis). T cells from 78 patients with generalised MG were stained with monoclonal antibodies against CD45RO, CD45RA, CD4 and CD8 and quantified by four-colour flow cytometry. The control panel for the prevalence analysis (a) consisted of 303 healthy individuals. (b) From those, 67 age- and sex-matched probands were randomly selected as controls for the subset analysis. Patients were stratified according to their MG onset age, thymic pathology and immunosuppressive treatment. Statistical analysis was performed by Fisher's exact test, asymptotic chi2 test, the two-sided Mann-Whitney test and Spearman's correlation coefficient. As a result, the 77C --> G mutation in exon 4 of the CD45 gene was found in 1 of 78 patients versus none of the 303 controls. Thus, no association was detected with this single nucleotide polymorphism in MG patients overall. Surprisingly, however, ratios of CD45RO+ to CD45RA+ T cells were lower among CD8+ T cells from patients with late-onset MG (P = 0.023). Thymoma patients also showed a similar trend among CD4+ and CD8+ T-cells, as expected. These differences were not related to immunosuppressive drug treatment or thymectomy (in the 67 informative patients). Since there is no other evidence for increased thymopoiesis in late-onset MG, we propose an altered subset balance in the circulation.
Tackenberg
B
B
Department of Neurology, Philipps-University, Rudolf-Bultmann Street 8, D-35033 Marburg, Germany.
Nitschke
M
M
Willcox
N
N
Ziegler
A
A
Nessler
S
S
Schumm
F
F
Oertel
W H
WH
Hemmer
B
B
Sommer
N
N
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009157:Myasthenia Gravis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D020033:Protein Isoforms; D017493:Leukocyte Common Antigens