Aa
Prime mover for MS lesions not autoimmune?
Australian study questions established concepts of early disease events in MS
http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=1100
This looks like an interesting article, in which researchers found little sign of immune cells in newly-developing lesions and instead noted a loss of oligodendrocytes (the cells that make myelin). This leads them to believe that it is not the immune cells (e.g., T cells, B cells) that directly cause MS lesions; rather they show up later. What strikes me is how little is still known about how the different aspects of MS work and are interrelated.
The researchers looked at "newly active and resolved lesions, as well as nearby blood vessels, surrounding areas showing some disease activity and surrounding areas that appeared normal, and areas that were farther away from the lesions of interest" in the brains of people with MS who had died.
"Results: In tissues surrounding newly forming lesions, the investigators found evidence of the loss of oligodendrocytes with an absence of immune T or B cells that would normally be held responsible for launching the immune attack against oligodendrocytes and the myelin they produce. These and other immune cells, including scavenger cells (macrophages and microglia), were more numerous in lesions and surrounding tissues at apparently later stages of destruction and sometimes in lesions that were in the process of repair. In specimens from two very early cases of clinical onset of disease, they found few immune cells within the lesions and no evidence of activation of scavenger cells.
"These and other unexpected findings from this study led the investigators to propose that the early immune activity seen in active lesions is that of macrophages and microglia, whose job it is to clean up and remove damaged myelin. They propose that lesion formation is caused by something other than destructive immune activity led by inflammatory cells against a component of myelin or oligodendrocytes."
From Pubmed: "INTERPRETATION: Early loss of oligodendrocytes is a prominent feature in tissue bordering rapidly expanding MS lesions. Macrophage activity is largely an innate scavenging response to the presence of degenerate and dead myelin. Adaptive immune activity involving T and B cells is conspicuous chiefly in recently demyelinated tissue, which may show signs of oligodendrocyte regeneration. The findings suggest that plaque formation has some basis other than destructive cell-mediated immunity directed against a myelin or oligodendrocyte antigen." (http://www.ncbi.nlm.nih.gov/pubmed/20035511)
At the end of the MSRC article is a plug for donating your brain to research, which is something to consider if you'd like to see scientists really answer these questions. Here are a couple thread discussing how to do this: http://www.medhelp.org/posts/Multiple-Sclerosis/OT--Morbid/show/1020613 and http://www.medhelp.org/posts/Multiple-Sclerosis/update-on-donating/show/1022177
sho
http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=1100
This looks like an interesting article, in which researchers found little sign of immune cells in newly-developing lesions and instead noted a loss of oligodendrocytes (the cells that make myelin). This leads them to believe that it is not the immune cells (e.g., T cells, B cells) that directly cause MS lesions; rather they show up later. What strikes me is how little is still known about how the different aspects of MS work and are interrelated.
The researchers looked at "newly active and resolved lesions, as well as nearby blood vessels, surrounding areas showing some disease activity and surrounding areas that appeared normal, and areas that were farther away from the lesions of interest" in the brains of people with MS who had died.
"Results: In tissues surrounding newly forming lesions, the investigators found evidence of the loss of oligodendrocytes with an absence of immune T or B cells that would normally be held responsible for launching the immune attack against oligodendrocytes and the myelin they produce. These and other immune cells, including scavenger cells (macrophages and microglia), were more numerous in lesions and surrounding tissues at apparently later stages of destruction and sometimes in lesions that were in the process of repair. In specimens from two very early cases of clinical onset of disease, they found few immune cells within the lesions and no evidence of activation of scavenger cells.
"These and other unexpected findings from this study led the investigators to propose that the early immune activity seen in active lesions is that of macrophages and microglia, whose job it is to clean up and remove damaged myelin. They propose that lesion formation is caused by something other than destructive immune activity led by inflammatory cells against a component of myelin or oligodendrocytes."
From Pubmed: "INTERPRETATION: Early loss of oligodendrocytes is a prominent feature in tissue bordering rapidly expanding MS lesions. Macrophage activity is largely an innate scavenging response to the presence of degenerate and dead myelin. Adaptive immune activity involving T and B cells is conspicuous chiefly in recently demyelinated tissue, which may show signs of oligodendrocyte regeneration. The findings suggest that plaque formation has some basis other than destructive cell-mediated immunity directed against a myelin or oligodendrocyte antigen." (http://www.ncbi.nlm.nih.gov/pubmed/20035511)
At the end of the MSRC article is a plug for donating your brain to research, which is something to consider if you'd like to see scientists really answer these questions. Here are a couple thread discussing how to do this: http://www.medhelp.org/posts/Multiple-Sclerosis/OT--Morbid/show/1020613 and http://www.medhelp.org/posts/Multiple-Sclerosis/update-on-donating/show/1022177
sho
Interesting angle on Schwann cell abnormalities. My friend/colleague had a huge benign Schwannoma removed, and when she had her initial MRI and follow-up MRI, she had lesions all over her brain that lit up like a Christmas tree with Gd. She has absoulutely NO MS symptoms. She's been followed up by a neurologist for the past 5 years every year, and still has no symptoms.
I had a smaller Schwannoma removed from my R middle finger back in '04. I have been diagnosed with MS.
So many questions...I hope they investigate the Schwann cell and Glioma angles.
I had a smaller Schwannoma removed from my R middle finger back in '04. I have been diagnosed with MS.
So many questions...I hope they investigate the Schwann cell and Glioma angles.
For those interested in this topic, here is an editorial by Peter Behan called "Futility of the autoimmune orthodoxy in multiple sclerosis research."
http://www.expert-reviews.com/doi/pdfplus/10.1586/ern.10.69
Not only does he argue that the autoimmune hypothesis is misguided, but he thinks that MS may be a cristopathy. I had to look this up, but apparently neuro cristopathy is "a disorder of neural crest derived cells" (http://download.journals.elsevierhealth.com/pdfs/journals/0039-6257/PII0039625789900143.pdf). There is an entry for neural crest cells on Wikipedia, but most of it went over my head: http://en.wikipedia.org/wiki/Neural_crest
He thinks that there should be more investigation of the association of MS with malignant glioma (type of brain tumor) and Schwann cell (support cells; they make myelin in the PNS) abnormalities in the peripheral nervous system and that researchers should look toward research in glial cells, cristopathies, and neurotrophic factors (things that support the health and feeding of neurons).
I had not heard of this idea before. It would be interesting to see a list of all the causes and mechanisms of MS that have been proposed.
sho
http://www.expert-reviews.com/doi/pdfplus/10.1586/ern.10.69
Not only does he argue that the autoimmune hypothesis is misguided, but he thinks that MS may be a cristopathy. I had to look this up, but apparently neuro cristopathy is "a disorder of neural crest derived cells" (http://download.journals.elsevierhealth.com/pdfs/journals/0039-6257/PII0039625789900143.pdf). There is an entry for neural crest cells on Wikipedia, but most of it went over my head: http://en.wikipedia.org/wiki/Neural_crest
He thinks that there should be more investigation of the association of MS with malignant glioma (type of brain tumor) and Schwann cell (support cells; they make myelin in the PNS) abnormalities in the peripheral nervous system and that researchers should look toward research in glial cells, cristopathies, and neurotrophic factors (things that support the health and feeding of neurons).
I had not heard of this idea before. It would be interesting to see a list of all the causes and mechanisms of MS that have been proposed.
sho
That's a very good question and I'm not sure anyone knows the answer. As you pointed out, scientists don't know how the DMDs work. They also don't know how MS works or what causes it.
I suppose the answer must have something to do with the fact that MS does have an autoimmune/inflammatory aspect and controlling that aspect prevents some of the damage associated with MS from occurring. However, if the autoimmune/inflammatory process isn't the underlying cause then that could explain why the DMDs are only moderately helpful.
It is fascinating. I just with they'd hurry up and put all the pieces together.
sho
I suppose the answer must have something to do with the fact that MS does have an autoimmune/inflammatory aspect and controlling that aspect prevents some of the damage associated with MS from occurring. However, if the autoimmune/inflammatory process isn't the underlying cause then that could explain why the DMDs are only moderately helpful.
It is fascinating. I just with they'd hurry up and put all the pieces together.
sho
This is fascinating research (and yes, I agree with saveone, I find it fascinating). What I was thinking of are the implications these findings have for the current treatment alternatives. We know scientists don't know for sure how the interferons, Copaxone and other treatments work: They have well-informed hunches but the exact way these drugs do their job (and why they work better in some people and cases than others) is largely unknown.
According to this research, then... how exactly do these drugs help to prevent new attacks? What are the implications of this work for our understanding of how the main drugs work???
According to this research, then... how exactly do these drugs help to prevent new attacks? What are the implications of this work for our understanding of how the main drugs work???
A REPOST FROM SHOSHIN
I don't think this study says anything about the likelihood of o-bands. It doesn't say that there are more or less inflammatory or autoimmune processes than previously thought, just that they come at a different point in the life cycle of an individual lesion.
However, it is true that o-bands are more likely to be normal early in the course of MS. Logically, this would seem to be because o-bands accumulate over time in people with MS. So early on, people would have had less time to accumulate them.
O-bands are not thought to disappear over time in MS, unlike with many other neurological diseases. This is why it doesn't matter if you are more or less symptomatic or in a flare or not at the time you have an LP.
I don't know if there are any other reasons why abnormal o-bands are less likely early on and it seems that no one else who read this post does either since there haven't been any other replies.
On the other hand, inflammatory, autoimmune activity is more predominant in early MS, which would seem to point to more rapid accumulation of o-bands early on. On yet another hand, I have never had any acute attacks and don't seem to have much inflammation, yet I had 13 o-bands when I had an LP. So I really don't know.
Anyway, as Quix often points, the LP is supporting evidence for MS and if your LP is normal, it doesn't mean that you don't have MS.
I don't think this study says anything about the likelihood of o-bands. It doesn't say that there are more or less inflammatory or autoimmune processes than previously thought, just that they come at a different point in the life cycle of an individual lesion.
However, it is true that o-bands are more likely to be normal early in the course of MS. Logically, this would seem to be because o-bands accumulate over time in people with MS. So early on, people would have had less time to accumulate them.
O-bands are not thought to disappear over time in MS, unlike with many other neurological diseases. This is why it doesn't matter if you are more or less symptomatic or in a flare or not at the time you have an LP.
I don't know if there are any other reasons why abnormal o-bands are less likely early on and it seems that no one else who read this post does either since there haven't been any other replies.
On the other hand, inflammatory, autoimmune activity is more predominant in early MS, which would seem to point to more rapid accumulation of o-bands early on. On yet another hand, I have never had any acute attacks and don't seem to have much inflammation, yet I had 13 o-bands when I had an LP. So I really don't know.
Anyway, as Quix often points, the LP is supporting evidence for MS and if your LP is normal, it doesn't mean that you don't have MS.
In 2001, I had a bone marrow transplant that stopped the progression of my MS and saved my life. If I hadn't had the transplant, I wouldn't be here right now. One thing I learned as they basically killed my immune system and regrew it, is that MS is a problem with the immune system, I am proof of that. I think it is more likely that whatever MS exactly is destroys oligodendrocytes as it attacks the myelin and suppresses the immune system from acting to save the body. I know this sounds like something that can't happen, but it makes sense. I think that MS is not one disease, but rather a couple acting together, or maybe one very nasty disease that just isn't being nice to me or anyone else with MS.
Justin
Justin
I'm new to this and may have completely misunderstood.
But would it mean that the results of an LP for OCB bands if done very early from the onset of MS symptoms would be more likley to come back normal?
But would it mean that the results of an LP for OCB bands if done very early from the onset of MS symptoms would be more likley to come back normal?
Here is a plainer English interpretation of this study, which looked at the pathology of lesions in the brains of people who had MS:
http://www.acceleratedcure.org:8080/node/3585
The main points seem to be
1. Some unknown factor is causing the oligodendrocytes (cells that make myelin) to die; this is followed by myelin breaking down
2. The T and B immune cells arrive later and thus don't seem to be the cause of the lesions or the myelin loss
3. The T and B cells are present during remyelination so it's possible that they are actually helpful
"The authors interpret their findings to indicate that plaques grow through loss of oligodendrocytes on the plaque border, which is followed by myelin breakdown, scavenging of debris by phagocytes, and infiltration of immune cells such as T cells. What causes the oligodendrocytes to die is not known -- for instance, it could be toxic elements seeping outward from the plaque, factors produced by activated microglia, or something else. The fact that T cells are not abundant in areas where phagocytes are actively scavenging myelin debris suggests that this process is not activated by T cells but instead is initiated by the macrophages themselves, similar to what is seen in injured tissue. The presence of T and B cells in greater numbers in recently demyelinated tissue indicates that these cells are part of the immune system's response to demyelination, as opposed to being a driver of the demyelination. Also, the fact that these cells are present where remyelination is taking place suggests that they don't prevent the regeneration process and may even help it."
sho
http://www.acceleratedcure.org:8080/node/3585
The main points seem to be
1. Some unknown factor is causing the oligodendrocytes (cells that make myelin) to die; this is followed by myelin breaking down
2. The T and B immune cells arrive later and thus don't seem to be the cause of the lesions or the myelin loss
3. The T and B cells are present during remyelination so it's possible that they are actually helpful
"The authors interpret their findings to indicate that plaques grow through loss of oligodendrocytes on the plaque border, which is followed by myelin breakdown, scavenging of debris by phagocytes, and infiltration of immune cells such as T cells. What causes the oligodendrocytes to die is not known -- for instance, it could be toxic elements seeping outward from the plaque, factors produced by activated microglia, or something else. The fact that T cells are not abundant in areas where phagocytes are actively scavenging myelin debris suggests that this process is not activated by T cells but instead is initiated by the macrophages themselves, similar to what is seen in injured tissue. The presence of T and B cells in greater numbers in recently demyelinated tissue indicates that these cells are part of the immune system's response to demyelination, as opposed to being a driver of the demyelination. Also, the fact that these cells are present where remyelination is taking place suggests that they don't prevent the regeneration process and may even help it."
sho
Me too! Like the one I posted the other day, it'll take me at least a week to go through the material and try to make some sense of it. This research stuff is so fascinating, and yet so beyond the capabilities of my little (scarred) pea-brain.
thanks Sho for sharing this one .... I do think there will be an answer to the cause of MS sometime in my lifetime.
I'll have to read this again and again to begin to understand this.
be well,
Lulu
I'll have to read this again and again to begin to understand this.
be well,
Lulu
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