You said “Could be a missing link into the trigger for MS”. Indeed there has been recent interest in the role of EBV as the cause of MS, and today the link is explained….or is it?
Someone else said “If EBV causes MS. Can it now be ruled out the MS isn’t an auto immune disease”
Here they looked at B cells in MS brain tissue and that some had been selected and expanded….presumably by disease. Then looked and many of the expanded B cells reacted with Epstein Barr Virus (EBV) and then they found a clone where the antibody reacted with a nerve protein and when animals were immunised against it disease got worse
It seems that an immune response to an EBV protein can cross-react with a brain protein to cause MS. This process is known as molecular mimicry where immunity to a pathogen cross-reacts with an protein to cause autoimmuniy. This study identifies glialcam as a cross-reactive target developing after EBV infection
If true then an idea that I put forward to explain autoimmunity after infection of B cells is incorrect.
However…let’s say hang on….. “molecular mimicry” is not a new idea and molecular micmicry between EBV and another brain protein anoctamin 2 (ANO2. On blood vessels?) was reported in 2019 and EBV and myelin basic protein in 1995 and now glialcam in 2022. What will be next?…..
Hopefully repetition because we have been here before, such as when MS was a result of antibodies to a potassium channel…It could not be replicated by others. So let’s see what happens and ask why didn’t they find reactivity to RASPRG2 another candidate last year or so. Maybe they did find it and just kept it quiet
What is Glialcam?
Glialcam is an adhesion molecule expressed by glial cells but the expression is high on astrocytes. So why MS and not Neuromyelitis Optica, which targets astrocytes. There is some expression on oligodendrocytes and furthermore, the gene name of glialcam is HEPACAM and was discovered as an adhesion molecule in…you guessed it…..hepatocytes…yep liver cells.
So why would you get a brain disease or would you expect the liver to be targeted in MS?
Lastly the question is is this the chicken or the egg? Is the immune response to Glialcam causing the damage or is it that damage caused by the cuase releases brain proteins that cause the glialcam response
If you want to read the paper search on the title and you will find a preprint. If you go to Nature look at the referees reports to get some insights.
Its not my idea, so we can let the authors of the work answer that one, indeed please come and send us a guest post on the work. Importantly, it will need to be repeated by other people, but a fantastic approach.
This manuscript suggets that EBV is a worthwhile target to control MS
Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM, Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system (CNS). B lymphocytes in the cerebrospinal fluid (CSF) of MS patients contribute to inflammation and secrete oligoclonal immunoglobulins. Epstein-Barr virus (EBV) infection has been linked to MS epidemiologically, but its pathological role remains unclear. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBNA1 and the CNS protein GlialCAM, and provide structural and in-vivo functional evidence for its relevance. A cross-reactive CSF-derived antibody was initially identified by single-cell sequencing of the paired-chain B cell repertoire of MS blood and CSF, followed by protein microarray-based testing of recombinantly expressed CSF-derived antibodies against MS-associated viruses. Sequence analysis, affinity measurements, and the crystal structure of the EBNA1-peptide epitope in complex with the autoreactive Fab fragment allowed for tracking the development of the naïve EBNA1-restricted antibody to a mature EBNA1/GlialCAM cross-reactive antibody. Molecular mimicry is facilitated by a post-translational modification of GlialCAM. EBNA1 immunization exacerbates the mouse model of MS and anti-EBNA1/GlialCAM antibodies are prevalent in MS patients. Our results provide a mechanistic link for the association between MS and EBV, and could guide the development of novel MS therapies.