Demyelination in Multiple Sclerosis (MS) results from an inflammatory process that appears to be immune mediated. The antigen(s) which initiate or sustain injury are unknown. We propose to characterize soluble immune complexes (ICx) that have been isolated from the cerebrospinal fluid (CSF) of patients with MS and other neurological disordes. Soluble ICx will be isolated in the fluid phase with ferritin conjugates of 125I-labeled monoclonal anti-IgG antibodies (anti-IgG-F). The high density of the ferrintin increases the effective s-rate of soluble ICx while its characteristic appearance simultaneously provides an ultrastructural marker for the ICx. Electron microscopy will be performed using negative staining techniques to improve macromolecular detail and with the hope that clues regarding the nature of putative antigens will be forthcoming, especially if relevant antigens are of viral origin. Antigen within soluble immune complexes will be analyzed utilizing polyacrylamide gel electrophoresis coupled with immunologic staining of """"""""blots"""""""" of protein separated by SDS-PAGE. Similar assays will be used to show the presence of antibodies within CSF that are directed to the individual protein bands. Finally, monoclonal antibodies will be raised to separated soluble ICx and screened for their reactivity with ICx and eventually the various bands separated by electrophoresis, again with the """"""""Western Blot"""""""" technique. By these studies, we hope to determine important physical and biochemical properties of antigens that may have pathogenic significance in MS and other neurological diseases. Ultimately, this should lead to new and specific strategies for immunotherapy.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology A Study Section (NEUA)
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University of Rochester
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