Antibodies to brain proteins accumulate in MS

Nazir FH, Wiberg A, Müller M, Mangsbo S, Burman J. Antibodies from serum and CSF of multiple sclerosis patients bind to oligodendroglial and neuronal cell-lines. Brain Commun. 2023 May 23;5(3):fcad164

Multiple sclerosis is a highly complex and heterogeneous disease. At the onset it often presents as a clinically isolated syndrome. Thereafter relapses are followed by periods of remissions, but eventually, most patients develop secondary progressive multiple sclerosis. It is widely accepted that autoantibodies (antibodies targeting your own body) are important to the pathogenesis of multiple sclerosis, but hitherto it has been difficult to identify the target of such autoantibodies. As an alternative strategy, cell-based methods of detecting autoantibodies have been developed. The objective of this study was to explore differences in the binding of antibodies from sera (blood) and CSF (spinal fluid) of multiple sclerosis patients and controls to oligodendroglial and neuronal cell-lines, related to antibody type, immunoglobulin (IgG/IgM), matrix (serum/CSF) and disease course. The oligodendroglial and neuronal cell-lines were expanded in tissue culture flasks and transferred to 96-well plates at a concentration of 50,000 cells/well followed by fixation. Sera and CSF samples, from healthy controls and multiple sclerosis patients, were incubated with the fixed cells. Epitope binding of immunoglobulins (IgG and IgM) in sera and CSF was detected…. Serum from 76 patients and 30 controls as well as CSF from 62 patients and 32 controls were investigated in the study. The binding was similar between clinically isolated syndrome patients and controls, whereas the largest differences were observed between secondary progressive multiple sclerosis patients and controls. Antibodies from multiple sclerosis patients (all disease course combined) bound more to all investigated cell-lines, irrespectively of matrix type, but binding of immunoglobulin G from CSF to human oligodendroglioma cell-line discriminated best between multiple sclerosis patients and controls with a sensitivity of 93% and a specificity of 96%. The cell-based enzyme linked immunosorbent assay (ELISA) was able to discriminate between multiple sclerosis patients and controls with a high degree of accuracy. The disease course was the major determinant for the antibody binding.

So as we make MS an antibody problem after it being years of a T cell problem, what does it say to me. Well it says what I know and that is people with MS harbour antibodies that react to nerve and myelin/oligodendrocyte expressed molecules and that people with MS have B cells in their brains that can produce antibodies, That they did not find much difference between health and early MS and found most differences with advanced MS again tells me that we are looking at the consequences of MS more than simple cause. However there are differences in early MS. As you get damage you liberate the contents of the damaged cells and these can cause the production of antibodies that react to the content. I know this happens as they have found the sequences of the antibody molecules and artifically made them and they react with stuff from inside the cell. In this study they are reacting the antibodies to fixed cells and there are more detected than healthy controls. I guess if they looked at unhealthy controls like people with brain disease they would also find antibodies to nerve and oligodendrocytes. It tells us there is brain disease. However it doesn’t tell us what they react to, but I could tell you some. It doesnt tell us what starts MS