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Brain-Reactive Antibodies and Disease

leokitten

Senior Member
Messages
1,541
Location
U.S.
We were discussing in another thread the possible (and very plausible) theory that if ME/CFS is autoimmune it could be that autoantibodies are being generated against parts of the brain and the damage or change in function they might cause would result in all the symptoms we experience. Here is a good introductory paper on the topic:

Brain-reactive antibodies and disease
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401150/

As I mentioned in the other thread, I believe that the major ME/CFS research groups should start spending at least some time/resources to study the autoimmune hypothesis, whether it's the above, or Fluge/Mella's current theory that autoantibodies might be generated that are interfering with vascular function, or other possibilities.

Lipkin/Hornig, Montoya, Younger, Davis/Kogelnik/OMF, none of the big groups have even opened to the idea of spending some of their resources to study autoimmunity in ME/CFS, even as more and more evidence has come out of Norway these last few years. @Sushi mentioned to me that KDM is currently working on his autoimmune hypothesis (see http://phoenixrising.me/archives/16017), although it is very different from the ones mentioned above, but at least he is thinking about it.
 
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Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
Lipkin/Hornig, Montoya, Younger, Davis/Kogelnik/OMF, none of the big groups have even opened the idea of spending some of their resources to study autoimmunity in ME/CFS, even as more and more evidence has come out of Norway these last few years.
I wouldn't expect all these groups to be thinking about autoimmunity, no more than I would expect my car's bodywork to be repaired if I dropped it in for a service.

Even if autoimmunity is found to cause ME in some of us, will it be the answer for everyone? No doubt there will be a join the dots exercise at some point but not all dots may belong to the same picture.
 

leokitten

Senior Member
Messages
1,541
Location
U.S.
Even if autoimmunity is found to cause ME in some of us, will it be the answer for everyone? No doubt there will be a join the dots exercise at some point but not all dots may belong to the same picture.

The results from Norway are continually showing that autoimmunity is likely playing a major (even causal) role in more than half of us. Even if it isn't the answer for everyone no other hypothesis to date has proven to affect such a large proportion of the ME/CFS population, in fact no other hypothesis to date has shown much of anything. I would say this should be enough evidence for the major ME/CFS research groups to at least spend some time/resources studying it.
 

Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
I'd certainly like to see at least one major group in the US studying autoimmunity in ME.

Thinking about practical treatment options alone, never mind learning more about the disease, it seems an odd omission - unless US insurers would be prepared to treat based solely on a successful Phase III in Norway.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Looks interesting - but a long read! I note that they state that the CNS has no lymphatic drainage system - a statement that may now need to be qualified.

@Jonathan Edwards

This may be of interest as they discuss B cell mediated autoimmunity (either of interest or as critique fodder).

I made it one third of the way through until my brain started hurting!
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
In light of the fairly recent Japanese study on microglial activation - this caught my eye (my bold) :

It is reasonable to ask whether failure to censor autoreactive B cells through central and peripheral tolerance mechanisms is more or less likely to occur for brain-reactive B cells. Exchange of soluble molecules and cells between the central nervous system (CNS) and other organs and compartments is highly restricted due to multiple mechanisms including the existence of the BBB (5). Recent evidence suggests that these mechanisms may be relatively well developed by the time the highly diverse B cell repertoire is generated (6,7); thus, it is likely that many brain-specific antigens are sequestered from immature or transitional B cells that are at a stage of maturation when they can still undergo negative selection and from post–germinal center B cells, which also undergo negative selection. This sequestration may explain why most brain-reactive antibodies appear to target antigens expressed by neurons or astrocytes rather than antigens expressed by microglia (CNS-resident myeloid cells), the latter of which are often also expressed by other myeloid-lineage cells and are therefore available to mediate negative selection of B cells. It is highly likely that neurons and astrocytes express a large number of antigens that are not appreciably expressed in other tissues or that they express a brain-specific isoform or a novel posttranslational modification of a more widely expressed antigen.
 

acer2000

Senior Member
Messages
818
I don't think that because some people felt better taking Rituxan that this means (by analogy) that ME/CFS is necessarily an autoimmune condition. I think what needs to be done is to figure out why people felt better after taking Rituxan. This should include a search for autoantibodies. But there could be other explanations.
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
Lipkin/Hornig, Montoya, Younger, Davis/Kogelnik/OMF, none of the big groups have even opened to the idea of spending some of their resources to study autoimmunity in ME/CFS,

Well, fortunately we have our three CFS Centers of Excellence staffed with a variety of clinical specialists and researchers to take on this work. I'm sure they are looking into this.

Oh wait. NIH closed them twelve years ago...
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I don't think that because some people felt better taking Rituxan that this means (by analogy) that ME/CFS is necessarily an autoimmune condition. I think what needs to be done is to figure out why people felt better after taking Rituxan. This should include a search for autoantibodies. But there could be other explanations.
In autoimmune diseases there is a six month lag for treatment because it takes time for antibodies to clear. The same lag occurs with Rituximab. Its not just about feeling better, including some who appear to have come very close to complete recovery or have actually achieved it.

On the other hand to prove an antibody based disease you need to identify the target at least, and preferably the target and antibody.
 

leokitten

Senior Member
Messages
1,541
Location
U.S.
I don't think that because some people felt better taking Rituxan that this means (by analogy) that ME/CFS is necessarily an autoimmune condition. I think what needs to be done is to figure out why people felt better after taking Rituxan. This should include a search for autoantibodies. But there could be other explanations.

I agree with @alex3619 comments, I think you are vastly understating the results of the now three studies from Norway. Rituximab didn't just make some people feel better, it made most people have a moderate or major improvement in all ME/CFS symptoms for a very long period of time. 1/3 of total where moderate responders and another 1/3 were major responders, and 1/4 of patients were still in complete remission 3 years later.

I know it can be difficult to read the results of the study and really connect and understand the impact Rituximab has had on patients without seeing them in person, but we should remember that not one other study in the history of ME/CFS research, not one, has been conducted with such rigor and shown such dramatic and repeated results as the three from Norway.
 
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geraldt52

Senior Member
Messages
602
As I mentioned in the other thread, I believe that the major ME/CFS research groups should start spending at least some time/resources to study the autoimmune hypothesis, whether it's the above, or Fluge/Mella's current theory that autoantibodies might be generated that are interfering with vascular function, or other possibilities.

Lipkin/Hornig, Montoya, Younger, Davis/Kogelnik/OMF, none of the big groups have even opened to the idea of spending some of their resources to study autoimmunity in ME/CFS, even as more and more evidence has come out of Norway these last few years.

I wondered about the seeming lack of interest as well but, playing the devil's advocate, I can also see where Lipkin, et al, may have concluded that the Fluge/Mella work is adequate for the task and they are content, for lack of a better word, to wait for the results of the current study. Having heard nothing but praise for the work of Fluge/Mella, I don't think it's unreasonable to think there is considerable respect for their work within the CFS research community.

I don't know that the other researchers could move things ahead any faster by preemptively jumping in with their own work at this time. We, and they, are all aware that research funds are very scarce, and maybe they are trying to be as efficient as possible by not risking duplicating the efforts of others at such an early point.