Saturday, 19 November 2011

Research: Identify of Oligoclonal bands

Yu et al. Intrathecally synthesized IgG in multiple sclerosis cerebrospinal fluid recognizes identical epitopes over time. J Neuroimmunol. 2011 Nov [Epub]

CSF =cerebrospinal fluid Plasma =blood fluid

Background: Intrathecal antibody production manifest as oligoclonal bands (OCBs) is a hallmark of multiple sclerosis (MS). Once present, OCBs can be detected in the cerebrospinal fluid that bathes the CNS throughout the lifetime of MS patients.

Aim:To determine the specificity of the OCBs, we applied CSF-derived immunoglobulins/antibodie (IgG) obtained from 2 consecutive lumbar punctures of 5 MS patients to screen random peptide libraries (a series of peptides that are the building blocks of proteins) and selected identical and related peptides that reacted with the paired CSF IgGs from each patient.

Results: Antiboies with the OCB reacted with pepetides and immunoblots also showed that these peptides were recognized by OCBs in MS CSF. We further demonstrated that the peptides represented linear epitopes, indicating that they represent natural epitopes of corresponding protein antigens. A database search combined with alanine scan mutagenesis of peptides that bound to CSF IgG from 3 MS patients revealed that they are derived from proteins including serine/threonine-protein kinase, protein ZIP2 and MHC class II (transplantation antigen)

Conclusions: Identification of targets that are recognized by IgG in MS CSF over time provides a critical tool to investigate the specificity of OCBs, which may determine the cause of disease, leading to strategies for diagnostic and therapeutic intervention.

The abilitity to identify what the OCB react to may give clues to the causative agent in MS if we can find they react with viruses, bacteria etc.

8 comments:

  1. Do OCBs always react to something? What do they react against in acute stroke?

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  2. Of course antibodies always react with something that is why they have
    a variable region or antigen binding region on each of their two arms, look at the structure of an antibody.

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  3. Thank you. What about the second question? Is it necessary that the react with something foreign to the body?

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  4. @Vasilis:

    The antibodies are reacting to the fatty materials that make up the plaque in the blood vessels. Researchers have recently discovered that people with low levels of antibodies against these fatty materials are at a higher risk of stroke: http://www.sciencedaily.com/releases/2010/02/100212101249.htm

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  5. It's come to the point where I find it hard to think that any question posed by Vasilis Vasilopoulos doesn't have an ulterior motive. (CCSVI, anyone?)

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  6. Dear Maria, i think you are talking about antibodies in the blood against the substances that cause arteriosclerosis.

    I am talking about OCBs found in the CSF of patients after acute stroke, after the brain damage caused by thrombi and the subsequent ischemia. This is a fact, anonymous, and has nothing to do with CCSVI. I just wonder what these antibodies are against. If they can form without foreign intervention, then perhaps OCB measurement as means of diagnosing MS could be abandoned and patients relieved from the need of spinal tap. After all, new, non-invasive, MRI-based metrics are available.

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  7. Second question. Do they have to react with something foreign to the body...obviously not if you read the post you could see that the OCB identified...were not foreign. Links were added so that you can read about the proteins identified and I assume you have heard of the MHC as this must have been mentioned in one of the MS gene linkage studies.

    If you look at wikipaedia for example

    http://en.wikipedia.org/wiki/Oligoclonal_band

    You will note that oligoclonal bands are not specific to MS this is why they are not totally diagnositic and there are MSers who don't have lumbar punctures as part of their diagnosis, because MRI has indeed aided diagnosis fantastically.

    Are the OCB produced in response to a direct stimulation to the target the antibodies are raised against is still an open question, alternatively are they a response of a mitogenic stimulation (i.e. the cell respond irrespective of their target being present) of something that stimulates B cells that happen to be in CNS. However there are pathogenic molecules from
    infectious agents that can be mitogenic or immortalizing to B cells in the CNS, could this cause of OCB.

    Pathologists are talking of B cell follicles (containing B cell plasma ce