Antibody specificity in neurological disease
The study of antigen-specific intrathecal oligoclonal bands is well established and a number of methods have been used to demonstrate that the relative affinity of the antibody produced in multiple sclerosis is low, and in encephalitis, high. A method colloquially known as Eastern blotting was developed whereby relative affinity of individual clones, rather than total antibody, could be studied and quantified by antigen immunoblotting and investigation of a digitised blot using image-manipulating software. This method was used to show that the pixel density of a band in CSF was significantly greater than the same band in serum in a patient with SSPE, and was thus of intrathecal origin. Eastern blotting was then used on a series of samples from a patient with herpes encephalitis to demonstrate that affinity maturation of the immune response had occurred intrathecally. The method was used qualitatively to investigate a proposal that Acinetobacter sp. infection could be the primary cause of multiple sclerosis: no evidence could be found to support the hypothesis. Another suggested cause of multiple sclerosis, Chlamydophila pneumoniae, was studied using a variety of methods including Western blotting. Again, there was no evidence to support the hypothesis. During the project, an unexpected effect of high-strength thiocyanate was revealed, and limited study of this suggested that thiocyanate had an effect on IgG, possibly related to the age of the sample.