Cerebrospinal fluid antibodies detect brain antigens

Abstract

Auto-immune destruction of central nervous system (CNS) antigens may contribute to the pathogenesis and prolonged clinical dysfunction in multiple sclerosis and other neurologic diseases. In an attempt to define relevant CNS auto-antigens, a sensitive assay (Enzyme Linked Immunosorbent Assay, ELISA) was developed, using as antigen, extracts of MS and control brains, and as antibody, cerebrospinal fluid (CSF). CSF from more than 80% of MS patients and less than 30% of control patients contained increased IgG anti-brain antibody levels. IgG₁ and IgG₃ were the predominant subclasses involved, but only IgG₃ demonstrated significantly more reactivity per μg antibody. Antibrain IgA and sometimes IgM levels were also elevated, but rarely IgD or IgE levels. Total reactivity to brain antigens rarely exceeded 0.1% of the antibody present. Total reactive antigen was extracted best with 1-butanol suggesting membrane association, and was extracted with similar efficiency from MS and control brains, from different areas of the same brain or from plaques or the corresponding periplaques from MS brains.