Wednesday, 20 February 2013

Have oligoclonal bands had their day?

#MSBlog: Do you have OCBs in your spinal fluid? It is helpful to know.

Kaplan et al. Free light chain monomer - dimer patterns in the diagnosis of multiple sclerosis. J Immunol Methods. 2013. doi:pii: S0022-1759(13)00034-3.

Background: In their search of new biomarkers for MS, these investigators aimed to characterize the immunoglobulin (Ig) free light chains (FLC) in MSers cerebrospinal fluid (CSF) and serum, and to evaluate the diagnostic utility of FLC monomer-dimer patterns for MS. 

Free light chains are one of the proteins that make-up immunoglobulins or antibodies.Light chains are made in excess to the heavy chains and are then referred to free light chains. They are a simple index of the amount of immunoglobulins or antibodies produced. There are two classes of light chain kappa (κ) or lambda (λ).


Methods: FLC were analyzed by Western blotting and mass spectroscopy. 

Western blotting = a laboratory method to separate proteins in solution based on the their size using charge or electrophoresis.

Spectroscopy = a laboratory method using light to detect various substances.

CSF and serum samples were examined for presence of oligoclonal Ig bands by a conventional laboratory test for MS. Three distinct pathological FLC monomer-dimer patterns, typical of MS but not of other neurological diseases, were revealed. 

Results: In 31 out 56 MSers the highly increased CSF levels of κ monomers and dimers were demonstrated. In 18 MSers, the increased κ-FLC levels were accompanied by highly elevated λ dimers. Five MSers showed no significant elevation in κ-FLC, but they displayed abnormally high λ dimer levels. The intensity of the immunoreactive FLC bands was measured to account for κ and λ monomer and dimer levels and their ratios in the CSF and serum. Combined usage of different FLC parameters allowed the determination of the appropriate FLC threshold values to diagnose MS. The developed method showed higher sensitivity and specificity (96% and 90%, respectively), as compared to those of the conventional OCB test (82% and 70%, respectively). 




Conclusion: This study highlights the role of the differential analysis of monomeric and dimeric κ- and λ-FLC for the precise diagnosis of MS.

"All  that this study iis showing that FLCs are a good supportive test to use when making the diagnosis of MS. They can't really talk aboout senistivity and specigicity until the have looked a larger number of people with other diseases. Finding an antibody or B cell response within the central nervous system is not unique to MS and occurs with several other diseases, in particular infections;  this is one of the reasons I think MS is caused by an infection."

"I believe that when we pin down the cause of MS we will find that the majority of antibodies in these bands will react against the inciting cause. I also predict that OCB negative MS will turn out to be a different disease."

"Did you know that the OCB negative MS has a better prognosis than OCB positive MS? Why?"

"Only about 2-5% of MSers are OCB negative; the one proviso here is that you have to be tested in a laboratory with the state of the art assay. Using old technology up to 35% are OCB negative."

"I would appreciate it if you could complete the following survey in relation to this post."

8 comments:

  1. If EBV or HERV turns out to be the cause of MS, why have they not been able to show that the oligoclonal bands bind to these? Are the bands in MS different to bands seen in other diseases/infections?

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    1. Good question, would like to know it as well, especially the first part. To my knowledge MS express OCB in a different way but I'll let the docs answer.

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    2. Have tried the EBV proteins! Not aware of any work on HERV proteins. Something to keep in mind for the future.

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  2. "..EBV-specific OCBs were detected in MS and in the other non-inflammatory and inflammatory demyelinating neurological diseases, with a similar frequency..."

    from:
    Cerebrospinal BAFF and Epstein-Barr virus-specific oligoclonal bands in multiple sclerosis and other inflammatory demyelinating neurological diseases.
    http://www.ncbi.nlm.nih.gov/pubmed/21109310

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    1. Thanks for this. I am aware of this data; unfortunately only a few bands react with EBV proteins. In comparison to known infections, for example measles encephalitis, the majority of bands react with the virus proteins.

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  3. Are state-of-the-art assays in common use? If the lumbar puncture was done in the 2000s in a US hospital, was it likely to have been state-of-the-art or old technology?

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    1. Not necessarily. A lot of US labs still use an old system (agarose gel). You need to find out if they are using isoelectric focusing (IEF) with immunofixation. There is a kit that has been FDA approved that is sold by Helena Biosciences:

      http://www.helena-biosciences.com/index.php?option=com_content&view=article&id=116&Itemid=346

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    2. thanks, I was able to find out which was used during my lumbar puncture, much appreciated

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