Fluorescent Protein Tracing in Multiple Sclerosis Brain Tissue

Abstract

SIXTY to seventy percent of patients with multiple sclerosis (MS) have an elevated cerebrospinal fluid (CSF) immunoglobulin-G (IgG) in the presence of normal serum IgG.1,2 These results prompted Kabat et al1 to suggest that IgG was synthesized in the brain. The results obtained by Frick and Scheid-Seydel,3 utilizing intravenous perfusion of radioactive IgG and albumin in a variety of patients, also suggested that the elevated CSF IgG in MS patients was derived from brain tissue or its coverings.Recently we reported4 for the first time that a positive correlation existed between the concentration of IgG in MS brain tissue (plaques of demyelination and surrounding normal-appearing white matter) and the IgG content of the CSF. In subsequent reports5,6 we suggested that the IgG in MS brain tissue was synthesized in the brain rather than derived from the blood because the blood-brain barrier appeared to be intact to smaller molecules (albumin and bromide). Furthermore, it appears from a cor¬ relative study of the histology and IgG con¬ centration in adjacent sections that IgG was synthesized by perivascular mononuclear cells or cells in the plaque, especially at its margin,7 or both. We have also suggested5·6 that the increased IgG in the normal-ap¬ pearing white matter was the result of dif¬ fusion of IgG from areas of synthesis.In this report we have attempted to local¬ ize more precisely the sites of synthesis of IgG in MS brain tissue. The IgG and albu¬ min distribution was estimated by inspec¬ tion of immunofluorescence in frozen-dried sections after incubation with fluoresceinconjugated antibody reagents. The pattern of distribution of specific fluorescence in and about MS plaque tissue was studied with respect to discernible histology as well as the histology revealed by hematoxylin and eosin-stained adjacent sections. Materials and MethodsIn an effort to minimize the loss of IgG from the tissue specimens, only quick-frozen unfixed tissues were employed. Antibody reagents of known titer were used to ensure antibody ex¬ cess, since the general range of concentration of IgG and albumin in the tissues studied was known beforehand (166 to 524

Measles and Other Virus-specific Immunoglobulins in Multiple Sclerosis

“…and the central nervous system is measles specific is not known, but, if the measles virus-specific globulin influences the neurological lesions of multiple sclerosis directly, it ought to be found in the IgG which is known to surround multiple sclerosis plaques in the brain (Simpson et al, 1969).…”

The possible viral aetiology of disseminated sclerosis1

“…Immunofluorescent study of MS plaques (Simpson et al, 1969;Lumsden, 1971;Tourtelotte, 1971) has also demonstrated IgG, IgM, and complement. According to Lumsden, the antimyelin activity of antibody is certain and it is well known that such antibodies present in the serum of MS patients can damage myelin in vitro (Bornstein and Appel, 1956;Lumsden, 1971;Tourtelotte, 1971).…”

A technique for the elution of cell‐surface antibody from human brain tissue

“…Similar methods may be applied to neurological disorders in which immunoglobulins are thought to be produced in the central nervous system. IgG is present at the plaque margin [6]. Washing brain sections resulted in a significant reduction of immunofluorescence, which indicated that the majority of IgG is unbound and perhaps located extracellularly [6].…”

“…IgG is present at the plaque margin [6]. Washing brain sections resulted in a significant reduction of immunofluorescence, which indicated that the majority of IgG is unbound and perhaps located extracellularly [6]. Whether the remaining IgG in MS brain is cell bound and produced in response to local antigenic stimulation has still not been determined.…”