Altered expression of costimulatory molecules in myasthenia gravis

To characterize the involvement of costimulatory pathways in the pathogenes is of myasthenia gravis (MG), a multiparameter flow cytometry assay was ado pted to enumerate blood mononuclear cells (MNC) expressing CD28, CD80, CD86 , CD40, and CD40L molecules in patients with MG and healthy subjects. Patie nts with MG had lower percentages of CD8(+)CD28(+) cells, augmented percent ages of CD4(+)CD80(+), CD4(+)CD86(+), CD8(+)CD80(+), CD8(+)CD86(+), CD14(+) CD80(+), and CD14(+)CD86(+) cells, and similar levels of cells expressing C D40 and CD40L and of B cells expressing CD80 and CD86 compared to the contr ols. Patients with early onset of MG (<40 years) had lower percentages of C D3(+)CD86(+), CD4(+)CD86(+), CD8(+)CD86(+) T cells and CD20(+)CD86(+) B cel ls compared to those with late onset (240 years). There was a positive corr elation between the patients' age and percentages of CD86(+) cells. The dat a indicate that the CD28/CD80-CD86 costimulatory pathway is involved in MG. The high percentages of CD80 and CD86 positive T cells and monocytes may r eflect persistent activation of T and B cells, whereas the low CD28 express ion may be the result of chronic exposure to CD80 and CD86. These molecules could be the focus for new and improved immunomodulating therapies of MG. (C) 2000 John Wiley & Sons, Inc.