What is the difference between relapsing and progressive MS. This new work from one of the number one science comics now tells us that it is due to immune cells responding to a grey matter protein called beta synuclein
Nature | Published: 20 February 2019
β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration
The grey matter is a central target of pathological processes in neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. The grey matter is often also affected in multiple sclerosis, an autoimmune disease of the central nervous system. The mechanisms that underlie grey matter inflammation and degeneration in multiple sclerosis are not well understood. Here we show that, in Lewis rats, T cells directed against the neuronal protein β-synuclein specifically invade the grey matter and that this is accompanied by the presentation of multifaceted clinical disease. The expression pattern of β-synuclein induces the local activation of these T cells and, therefore, determined inflammatory priming of the tissue and targeted recruitment of immune cells. The resulting inflammation led to significant changes in the grey matter, which ranged from gliosis (proliferation of astrocytes) and neuronal destruction to brain atrophy. In humans, β-synuclein-specific T cells were enriched in patients with chronic-progressive multiple sclerosis. These findings reveal a previously unrecognized role of β-synuclein in provoking T-cell-mediated pathology of the central nervous system.
In the study they take myelin basic protein responsive CD4 T cells and cells that react to B synuclein. These can be tracked as they go from injection to lung to lymph gland.to spleen to blood and then the central nervous system, forgetting to go past the git for that microbiome feeling.:-).They both arrive on the outside of the the CNS tissue and the MBP cause damage to the white matter (on the outside of the spinal cord) and the synuclein cells cause damage to the grey matter which is on the outside of the brain.So what happens in MS?
People with progressive MS have more reactivity to alpha and beta synuclein.
So they you go.
In yesteryear I would be straight down the lab to see if I can repeat this stuff, but now I will let others do it.
We have been here before. Time and time again.
Here MBP responsiveness is more in MS than controls. There are plenty of studies showing there is no difference between the number. Maybe the quality of the response
So should we believe the result that the response to these nerve proteins are more common in progressive MS?
But is this a cause or a consequence of damage? You have nerve damage and that liberates nerve proteins to which the immune response can generate.
Many years ago we tried to induce EAE with grey matter and got nothing, although it switched off white matter disease. However, if you can get a T cell reactive to a grey matter antigen, you can get EAE with grey matter involvement. Just as you can get astrocyte targeting with an astrocyte antigen. There is not as much beta synuclien in the spinal cord so why not infiltrate the brain. Then you can do losts of imaging etc and cytokine analysis etc. But we know rat EAE in most of its guises is T cell mediated. But………
I ask one question
What is the response to therapy in humans?
This is the question that we should always think about. If we look at the graphs there are plenty of humans with a low response.
So is the observation universal or is it the odd few that make it interesting. It will now be repeated in other labs ….or it will not be repeated, this is not unusual for this science comic.
Now back to the question. What is the treatment response in humans.?
Does depletion of CD4 T cells halt progressive MS, which it surely would if this were true and important?
Did all those people taking alemtuzumab and HSCT during secondary progressive MS with massive T cell depletion have no cognitive decline in trials and did they stop progression.
If we follow the logic created, that response to alpha synuclein is associated with Parkinsons
Do people with MS get early Parkinsons disease?
Have it for your homework for the weekend. I will guess the answer(s), can you? 🙂