Showing papers by "Arthur A. Vandenbark published in 1984"

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.

Brain antigens detected by cerebrospinal fluid from multiple sclerosis patients

Abstract: Increased levels of antibodies against both multiple sclerosis (MS) and control brain extracts were observed in the cerebrospinal fluid of MS patients using a sensitive assay (Enzyme Linked Immunosorbent Assay, ELISA). The possibility that antibodies in MS CSF can detect ‘MS associated’ brain antigens was examined by testing various CSFs for reactivity against chromatofocused fractions obtained from MS or control brain extracts. The MS CSF showed increased reactivity against many of the chromatofocused fractions, indicating the presence of a broad spectrum of antigens in the various brain extracts. However, quantitative differences in reactivity against various fractions were observed, resulting in reproducible reactivity patterns of CSF against various brain extracts. A comparison of these reactivity patterns revealed that the same MS CSFs recognized the same regions (roughly nine in all) in the separation profile of two MS brain extracts. The MS CSFs showed significantly less reactivity against five of these regions from normal brain, but against only three regions from a Huntingtons brain extract. Reactivity to two regions of the MS brain extracts was significantly reduced to both normal and Hunting-tons brain extracts. Whether these quantitative differences in the reactivity patterns reflect qualitative differences in the fractions will be analysed further by preabsorbing reactive CSFs on normal brain fractions to remove antibodies directed against identical or cross reactive antigens.

Antibrain antibody adsorption on microtitre plates

Abstract: Low concentrations of antibrain antibody can be detected in cerebrospinal fluid (CSF) from most patients with multiple sclerosis and a few patients with other neurologic diseases.

Shared antibrain specificities of cerebrospinal fluid and synovial fluid antibodies

Abstract: Both the cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients and synovial fluid (SF) from rheumatoid arthritis (RA) patients demonstrate increased lymphocyte infiltration and production of immunoglobulin of multiple specificities. To explore the possibility that antibodies present in these widely separated compartments share similar or identical specificities, reactions of CSF and SF with extracts of brain and synovial tissue or with purified antigens were compared by the enzyme linked immunosorbent assay (ELISA). CSF and SF showed significant reactivity to both of the tissue extracts as well as to myelin basic protein (MBP) and keyhole limpet haemocyanin (KLH). The reactivity to MBP of CSF and SF was inhibitable by preincubation with specific rabbit antibody, suggesting that the same or closely associated determinants were recognized by antibodies in both fluids and by the rabbit antibodies. In additional experiments, reactivity of pooled CSF or SF to chromatofocused fractions of brain or synovial tissue extracts revealed similar reaction patterns, although each fluid reacted distinctly with at least one fraction of each extract. These results support the suggestion that a common deregulation process in MS and RA stimulates non-selectively a large repertoire of B-cell clones to produce ‘nonsense’ immunoglobulins to many antigens, including some presumably not found in the respective tissue compartments. Responses to disease-associated ‘target’ antigens are difficult to discern, but may be detectable in CSF or SF reactions to fractions of crude tissue extracts.