Altered expression of costimulatory molecules in myasthenia gravis

• Published in: Muscle & nerve Vol. 23; no. 6; pp. 946 - 953
• Main Authors: Teleshova, Natalia, Matusevicius, Darius, Kivisäkk, Pia, Mustafa, Maha, Pirskanen, Ritva, Link, Hans
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01-06-2000; Wiley
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, CD - analysis; Antigens, CD - biosynthesis; Antigens, CD - immunology; Autoantibodies - blood; B-Lymphocytes - chemistry; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B7-1 Antigen - analysis; B7-1 Antigen - biosynthesis; B7-1 Antigen - immunology; B7-2 Antigen; Biological and medical sciences; Biomarkers; CD28 Antigens - analysis; CD28 Antigens - biosynthesis; CD28 Antigens - immunology; CD28/CD80-CD86; CD40 Antigens - analysis; CD40 Antigens - biosynthesis; CD40 Antigens - immunology; CD40 Ligand; CD40/CD40L; costimulatory molecules; Diseases of striated muscles. Neuromuscular diseases; Female; Flow Cytometry; Humans; Male; Medical sciences; Membrane Glycoproteins - analysis; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - immunology; Middle Aged; myasthenia gravis; Myasthenia Gravis - diagnosis; Myasthenia Gravis - immunology; Myasthenia Gravis - metabolism; Neurology; Receptors, Cholinergic - immunology; T-Lymphocytes - chemistry; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Antigen; Human; Flow cytometry; Neuromuscular diseases; Nervous system diseases; Correlation; Mononuclear cell; Myasthenia gravis; Pathogenesis; T-Lymphocyte; B-Lymphocyte; Gene expression
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/(SICI)1097-4598(200006)23:6<946::AID-MUS16>3.0.CO;2-4

To characterize the involvement of costimulatory pathways in the pathogenesis of myasthenia gravis (MG), a multiparameter flow cytometry assay was adopted to enumerate blood mononuclear cells (MNC) expressing CD28, CD80, CD86, CD40, and CD40L molecules in patients with MG and healthy subjects. Patients with MG had lower percentages of CD8+CD28+ cells, augmented percentages of CD4+CD80+, CD4+CD86+, CD8+CD80+, CD8+CD86+, CD14+CD80+, and CD14+CD86+ cells, and similar levels of cells expressing CD40 and CD40L and of B cells expressing CD80 and CD86 compared to the controls. Patients with early onset of MG (<40 years) had lower percentages of CD3+CD86+, CD4+CD86+, CD8+CD86+ T cells and CD20+CD86+ B cells compared to those with late onset (>40 years). There was a positive correlation between the patients' age and percentages of CD86+ cells. The data 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 reflect persistent activation of T and B cells, whereas the low CD28 expression 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. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 946–953, 2000