Monoclonal Autoantibodies Derived from Multiple Sclerosis Patients and Control Persons and Their Reactivities with Antigens of the Central Nervous System

Abstract

Peripheral blood B lymphocytes of multiple sclerosis (MS) patients and control persons were transformed with Epstein-Barr virus. Antibody production of transformed cells against isolated human myelin was investigated by enzyme-linked immunosorbent assay (ELISA). Cells producing reactive antibodies were cloned and propagated to produce monoclonal antibodies (mAbs). These mAbs did also react with acetone fixed frozen sections of normal human white matter, as determined by indirect immunofiuorescence staining. Some of the mAbs derived from MS patients and a control person with a central nervous system cyste agglutinated liposomes made from lipids of a chloroform/methanol extract of human myelin, whereas mAbs derived from four glioma patients were negative in these tests. The reactive antibodies were investigated further using agglutination tests with liposomes made from pure auxiliary lipids (cholesterol and lecithin) or containing in addition either galactocerebroside, sulfatide or a mixture of bovine brain gangliosides. The great majority of myelin liposome agglutinating antibodies reacted with all types of liposomes, including those made from pure auxiliary lipids. Investigations by ELISA suggest that phospholipids are the reactive components, at least for some of these mAbs. Some antibodies reacted with liposomes containing galactocerebroside or sulfatide, others only with sulfatide containing liposomes. Antibodies showing these specificities were only obtained from MS patients.

Key Words:

• Autoantibodies
• multiple sclerosis
• anti-myelin
• glycolipids
• phospholipids
• human monoclonal antibodies