Autoantibodies and the cytoskeleton

Mead, Graham Michael (1980) Autoantibodies and the cytoskeleton. University of Southampton, Doctoral Thesis.

Abstract

This study describes measurement of antibodies to the cytoskeleton in man using a variety of fluorescent techniques and subsequently a radioimmunoassay. Initially indirect immunofluorescence using a rat tissue substrate was employed. This technique, though widely clinically used was found to lack both specificity and sensitivity. The subjective reporting of samples is an additional disadvantage. A study in patients with malignant disease showed no increased incidence of autoantibodies. Subsequent studies employed a fixed tissue culture cell substrate. This technique increased sensitivity but specificity remained poor. A radioimmunoassay was developed for the measurement of antibody to tubulin, a microtubule component protein. Using this highly specific technique it was possible to detect antitubulin antibody in all members of a healthy control population. Elevated antibody levels were detected in a number of diseases, but particularly in infectious mono-nucleosis. An affinity chromatography purified antitubulin antibody was produced from this source.Rabbit immunization with actin and tubulin failed to resultin detectable increases in antibody levels to these antigens. Of particular note was the finding of cytoskeletal antibodies in most animals pre-immunization. The reported incidence of autoantibodies is related predominantly to the sensitivity of the technique involved in their evaluation. Radioimmunoassay would appear to be a suitable tool for such studies in the future.

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