1. MS has not be seen in people who don’t make immunoglobulins due to rare genetic disorders (agammaglobulinaemia).
2. Oligoclonal IgG bands are invariably found in the cerebrospinal fluid (CSF) and brain/spinal tissues of MSers. These immunoglobulin bands have been highly selected; in other words whatever is driving their production is getting help from other cells (antigen presenting cells and T cells). This selection process is typically seen with infections or foreign antigens (proteins).
“In my opinion if we can uncover what these bands are reacting with we will uncover or pin down the cause of MS”.
“In my opinion OCB-negative MSers don’t have ‘classic MS’ and should be given a separate diagnosis or the diagnosis of definitive MS should be delayed; this is particularly important when diagnosing PPMS! This is another reason why lumbar punctures and spinal fluid analysis should be done in all MSers. You only get one chance not to make the diagnosis of MS and that is in the beginning or the diagnostic phase of the disease. Spinal fluid analysis helps you exclude other conditions and tells you if you have OCBs or not.”
“Could the B cell be the Trojan horse that takes EBV into the brain and spinal cord? Unfortunately, the evidence on this topic is rather mixed at present, but I suspect the B-cell is the cell that EBV hitches a ride in.”
“This is an observation that I made years ago!”
“It is a pity that anti-CD20 therapies do not target plasma cells or plasma blasts; these are the immunoglobulin factory cells and are also part of immunoglobulin pathway. May be the newer anti-CD19 agents that target plasma blasts will be more effective than anti-CD20?”
The Grand Challenge: “Are B cells the pivotal cell in the pathogenesis of MS? How do anti-B cell therapies work in MS? Do anti-B cell therapies work as anti-EBV agents?”
Other posts of interest:
Ocrelizumab:
Rituximab:
CoI: multiple
Prof G can you please tell us about anti-CD19 treatment? Is there any way of getting on to it?
Posted: http://multiple-sclerosis-research.blogspot.co.uk/2012/11/anti-cd19-and-multiple-sclerosis.html
Are you participating in the MS Society's project to identify unanswered questions in MS in association with the James Lind Alliance? Maybe some of your Grand Challenges would be good questions to ask on that forum. Details are on MSS website – though hopefully you know about it already.
Thanks for the advice. This is the first I have heard about this initiative. I will look into it. This is unrelated to our Grand Challenges; I thought I would start this section of the blog after reading about the grand research challenges initiative the NIH in the US launched for science in general. I did it to break up the endless research posts and generate a bit of debate. What I am really hoping for is for a fairy godmother or angel to fund one of these challenges.
– If the MS diagnosis was made years ago without doing an LP, is there any point in asking for one now? The MS has been aggressive and nobody doubts the diagnosis- With a drug that targets plasma cells too, will there be a high chance of serious infections?- I remember reading there is disagreement about ectopic B-cell follicles in MSers. Can you write more about that?
There is indeed disagreement about B cell follicles. Many who have looked for them can't find them and I can't believe that they would not have been noticed before if they were a common feature.
yes a drug that takes out the whole B cell lineage may cause problems with immune suppression. The good thing about this is that it is easy to correct; all you need to do is give immunoglobulin therapy, a large number of people have this problem.
Can any kind of brain damage trauma, infarcts, infections – to the least degree metabolic anomalies cause the same spectrum of oligoclonal banding, i.e. immune reactions, as multiple sclerosis.? and are they seen as the same in the EAE model?Regards as always.
Nothing ?
No not in typical stroke. However, if the stroke is due to an vasculitis (inflammation in the blood vessel walls) or infection (varicella-zoster virus) then you can get OCBs. OCBs are non-specific an occur in a large number of inflammatory disorders of the brain and spinal cord. The conditions associated with OCBs are usually easy to diagnose and differentiate from MS. You also find OCBs in a small number of normal people; these people have presumably had a mild episode of encephalitis or they could be at risk of MS.
You say that most things that cause OCBs are easy to differentiate from MS. What sort of things are not so easy to differentiate? Sjogren's? Neurosarcoidosis?
Sjogren's and sarcoid are typically not associated with OCBs. I have written an article on this before. Paraneoplastic disorders and infections are the conditions associated with OCBs.
Why I'm taking an interest in 'O' bands is my wife's Neurologist waited for the results of the lumbar puncture before dx and seemed to deem her to have mild MS based on these, so I'm reading up on the significance.Sine reading I've come across an old paper and would like your thoughts ."Cellular immune response to myelin protein: Absence in MS and presence in cerebrovascular accidents,Youngchaiud U et al. 1974
Any idea (a timeline?) when some of these Grand Challenges will be resolved i.e. answered. It seems simple to keep generating questions, but much more difficult to answer them!I'm guessing the Charcot Project may answer the EBV question – or will it just generate more questions / more research?Any idea when will get more results from the B cell depleting trials? Why isn't Alemtuzumab called a B cell depleting therapy? (I thought it targetted B cells?).I'm really looking forward to the day when answers to these big questions will be posted on this blog. It's all taking far too long for those already with the disease. Hopefully 2013 will see some real progress, but I'm sure I hoped for this in 2012.I'm in two minds about attending the Research Event. Will I hear anything new? Anything to give me hope for the near future?Best of luck.
2012 is meant to be the year that alemtuzumab got a license for MS. It is the only drug one the near horizon that offers a potential for a cure. The others are cladribine and bone marrow transplantation. The latter is too dangerous to be a mainstream treatment.
Will I hear anything new? Anything to give me hope for the near future?Yes
Which? Something new (genuinely new and not been announced/covered elsewhere?) or just "yes" to anything to give hope for the future?
"It is clear that B cells play a central role in pathogenesis of MS:"from:B cells and autoantibodies: complex roles in CNS injury.http://www.ncbi.nlm.nih.gov/pubmed/20691635"Emerging data indicate that traumatic injury to the brain or spinal cord activates B lymphocytes, culminating in the production of antibodies specific for antigens found within and outside the central nervous system (CNS)."A lesion is an injury of some kind. B-cell presence is, once again, the result, not the cause. The antibodies produced do not point to the damaging agent, they are just the "system scan" initiated by the injury.
So in MS what would be the "traumatic injury" triggering a B cell response? I think I already know what your answer is going to be but who knows you may surprise me.
That's for researchers like you to find out. The study shows that a different explanation for the antibody presence is possible. Since you (researchers) had no luck yet in pinpointing the target or the trigger of the immune response, why don't you try studying the problem from a different perspective. You claim to have an open mind.
We (researchers) have found plenty of targetsMay have an open mind but but don't have bottom less pockets, ideas may grow on trees but unfortunately investigating them doesn't