Evidence against oligoclonal bands being important?

As you may realise, I am sometimes critical of my colleagues who tend to follow dogma, without question.

This of course does me no favours with my colleagues. Maybe I should just say everything is “Great” or “Super”, like I’m part of  some 1970s Sitcom :-0

For many, many years my colleagues have been hunting for the autoantigen in MS. They have got nowhere fast and we have seen more false dawns than I’ve had tequila sunrises.

MD2 has stuck his neck out and has suggested that we are wasting our time hunting for the causative antibody.

Indeed MD2 has suggested that the antibodies produced in the CNS are not inert and that they may simply bind to microglia via their tails rather than their heads that bind to their targets. These would serve to stimulate the microglia possibly to maintain a damaging phenotype that could drive degeneration in damaged nerves.


Pryce G, Baker D. Oligoclonal bands in multiple sclerosis; Functional significance and therapeutic implications. Does the specificity matter? Mult Scler Relat Disord. 2018;25:131-137.

So you set up an idea and you don’t try to prove it but you try to disprove it. This is called Popperian Science, after Karl Popper.

Therefore, thanks to one of the readers who did some reading and found this paper. 

It is a case of some one with MS who had a B cell cancer. They were given a stem cell cell transplant (HSCT) and they became oligoclonal band negative. However, disease activity continued.

Therefore, oligoclonal bands can’t be a driver of progression, can they?


BACKGROUND:Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases.
AIMS:To describe the effects of allo-HCT on the course of MS in a 49-year-old woman with longstanding progressive MS who was treated with allo-HCT for follicular lymphoma.
METHODS:Non-myeloablative conditioning allo-HCT, examination for IgG oligoclonal bands and measurement of CXCL13 and matrix metalloproteinase-9 (MMP-9) concentration in the cerebrospinal fluid (CSF).
RESULTS:Despite the disappearance of oligoclonal bands in CSF, disease progression and CSF inflammation was observed.
CONCLUSIONS:We hypothesize that CXCL13 and MMP-9 detected in CSF may reflect ongoing, pathogenic immune activation even after the eradication of intrathecal IgG synthesis. This suggests that progressive MS may depend more on innate than on adaptive immune activation.

Maybe, but we have to figure out what could be happening before we give up on the idea. In this study the person had a B cell lymphoma and is treated with cyclophosphamide (CNS penetrant) and fludarabine (CNS penetrant) immunosuppressive agents capable of killing dividing (B) cells. The lymphoma is put under control and the person does a stem cell transplant. 

The transplant then starts to attack the body (Graft verses host disease). This means that the graft will attack anything that expresses transplantion antigens called the human leucocyte antigens (HLA) or major histocompatibility complex (MHC) antigens. 

B cells express high amounts of both class I and class II MHC and so will be targeted by the new immune system coming from the transplant. This could easily destroy B cells in the CNS that produce oligoclonal bands, especially as the MS would have made the CNS more leaky to immune cells. Also because of the MS, nerve cells sometimes express MHC class I and so could get attacked and damage too.

Indeed the graft immune system can target and kill any host cell expressing MHC class II and MHC class I antigens. These (MHC class I) are expressed by the skin and other tissues, which why the graft verse host disease occurs can be easily visible (I’d show you a picture but it is rather gross and will put you off your food). 

To treat this the person gets more immunosuppression  (cyclosporin A, mycophenylate) including anti-TNF. This latter agent has been associated with triggering the development of MS in some people.

This person started developing new lesions (i.e. sub-clinical relapsing MS), but when tested they had become oligoclonal band negative. But would this mean that the cells causing graft verses host disease were entering the CNS and causing damage. Could this be the cause of the lesions? However, it could certainly cause the production of cytokines that keep microglia activated, meaning that you don’t need oligoclonal bands to do this job.

However, the the person was having spinal cord lesions and their movement got worse.  They got graft verses host disease again and this goes chronic for months before it is put under control. 

Then the person gets tacrolimus, or FK506, which is an immunosuppressive agent. Although this may have neuroprotective potential,  it can also cause neurological problems in some people. Is this part of the problem and the worsening of neurological problems for this person? I don’t know. However there are a lot of confounding possibilities so that we can not be sure if this kills off the B cell ideas.

The idea but forward by MD2 was that activated microglia may be a central part of progressive MS. There are probably different routes to achieve this.  In this study they find CXCL13 (CXCL13 is a small chemokine  that chemokine is selectively chemotactic for B cells , such as memory B cells, by interacting with chemokine receptor CXCR5) and MMP9 (a metalloprotease associated with inflammation) Would we want this.

Do you have any ideas, I may be talking tosh.

Keep the anti views coming.

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  • Oligoclonal bands are not specific to MS – how do we explain that? Also are oligoclonal bands the same between different patients or does everybody have a unique sets of bands?

    • B cells enter the CNS in other conditions and form a plasma cell niche and oligoclonal bands. Activated microglia are at the centre of many other CNS conditions. No oligoclonal bands are not generally the same between differen people, perhaps arging that their specificity is not important.

  • Some people lose OGB after HTSC but some gain them..not sure..???

    "In a study of 20 patients, 9 out of the 12 patients having OCB before HSCT were still positive after, and one OCB-negative patient at baseline gained OCB [96]. In a review of 34 HSCT patients, OCB persisted in 30/34 patients while 2 out of the 10 who were initially OCB-negative became positive"

    "Intrathecal IgG synthesis is present in almost every MS patient unlike other CSF markers, which are elevated only in a subset of patients. For example, mean levels of common markers like soluble sCD27 (a marker of T-cell activation), neurofilament light-chain (marker of neurodegeneration), and CXCL13/CXCL10 (attractive cytokines for B-cells) are all elevated in MS series but remain normal in a large proportion of individual MS patients. On the other hand, IgG synthesis (BOC or IgG index) is always elevated in MS patients and intrathecal IgG level normalization is a goal yet to be attained with treatments. Moreover, a major decrease in intrathecal IgG synthesis, which recapitulates the terminal function of Ig-secreting cells, should be more predictive of an intraparenchymal depletion of the B-cell population."


  • I am also a physician with MS, 10 years now.
    Primary progressive. Despite having lesions in the Brain and SC,
    there were no Oligoclonal bands found in the CNS.
    However, there was a large collection of Neurofilament Fragmentation, that helped seal my diagnosis, through quantifiable diagnostic criteria.

    I am clearly not a fan of the Oligoclonal Band Theory
    as a strict criterium.

    Much Appreciated.

    J.M. Jackson MD

  • The Wheelchair KamikazeWednesday, August 01, 2018 8:50:00 am

    A Nonny Moose – For what it's worth, I am also OCB negative and have had a progressively worsening disease path ever since diagnosis (actually from before diagnosis). I believe Dr. G has stated that he thinks OCB negative patients may not have ms.

    In my case, if I do have ms it is a highly atypical form, as I've only ever had to lesions (one big juicy monster right at the base of my brainstem, and a smaller much less significant one in the right Periventricular region) which haven't changed in any way at all since my first MRI images were done over 15 years ago. Despite this, and the lack of OCB's, I've gone from walking with a tiny limp in 2003 to having my entire right side paralyzed and my left on its way to join the right 15 years later.

    Would be nice to know if people like you and I do indeed suffer from some other malady… We are in such a minority, though, that not much attention is paid…


  • The contradiction between the lower number of CNS cells (about 3.5 million cells in MS CSF) and higher levels of intrathecal IgG (10 mg/day), combined with the evidence that there is no correlation between plasma cells and Gd-enhancing lesions in MS, raise the question as to whether B cells in MS CNS can be responsible for the massive amounts of elevated intrathecal IgG. Tourtellotte calculated that it would take 3.2 billion lymphocytes in MS to generate such large amounts of CNS IgG, therefore circulating MS CSF lymphocytes could only account for <0.1% of the extra IgG in the CSF. This apparent knowledge gap suggests that most of the intrathecal IgG in MS may actually be derived from the blood.

    The complex relationship between oligoclonal bands, lymphocytes in the cerebrospinal fluid, and immunoglobulin G antibodies in multiple sclerosis: Indication of serum contribution


  • Do you want everyone with a diagnosis of MS and no Oligoclonal bands to post on here. I have much more typical MS than the Wheelchair Kamikaze (diagnosed 18 years ago, plenty of brain lesions then, more now, a slightly odd walk then, in a wheelchair most of the time now). But, like him, I have no Oligoclonal bands. My neurologist tells me he is "sure" I have MS, and it seems to me he is right.

  • I believe that it creates a source of confusion for both patients and physicians.Trying to validate certainty in an often illusive, diagnosis of exclusion disorder, that culminates for many, including myself as a physician/patient, to doubt about the diagnosis. Fortunately, with the advent of other diagnostic tools, like the MRI for example, and a willingness by physicians to listen to their patients in regards to their symptoms, and monitoring their clinical course carefully, places less importance on a test such as the presence or not of bands found on a CSF sample.It also,reinforces my own personal
    belief that "MS" is still a mystery to even the most knowledgeable about the disease.

  • Meant to say: Do you want everyone with a diagnosis of MS and no Oligoclonal bands to post on here?

  • I have no oligoclnal bands and another very atypical MS which since 2001 has only presented as sensory symptoms and one major relapse but no lasting effect, returning back to baseline. Not on any DMTs. I have dedicated my existence to lifestyle modification for over two years now but the question of what is the nature of this beast still follows me every day.

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