Research: Virus in the CSF

Kułakowska et al. Multiplexing analysis of the polyspecific intrathecal immune response in multiple sclerosis.Methods. 2012 Mar 16. [Epub ahead of print]

Intrathecal synthesis of the antibodies specific to neurotrofic viruses: measles (M), rubella (R), Varicella-Zoster (Z), and/or H. simplex (H), known as “MRZH-reaction” plays important diagnostic role in multiple sclerosis (MS). Whereas the analysis of the oligoclonal IgG bands provides high sensitivity, the MRZH-reaction shows high specificity, and hence these methods complement each other. For the first time we applied multiplexing bead-based technology to simultaneously analyze cerebrospinal fluid (CSF) and serum concentrations of antibodies against these viruses, and to calculate the antibody specific indices (ASI’s). The method shows reasonable precision: intra-assay, 2.9-6.7%, and inter-assay, 2.0-3.2%. The results are comparable with these obtained with other methods (ELISAs), including two runs of the certified external quality control schemes. Eighty-one percent of the MS cases (n=27) and none of the sex- and age-matched controls (n=14), except one subject with “borderline” anti-measles ASI of 1.5, showed intrathecal synthesis of IgG against at least one of the viruses discussed. The ratios of the MRZH-positive cases in the MS group were: 12/22 for M, 12/19 for R, 13/26 for Z, and 7/26 for H. We conclude that the multiplexing technology can be applied as a tool to study the intrathecal immune response in the diagnosis of MS.

Viruses have been associated as a trigger factor of MS, but it may not always be the same virus and so assaying form more than one at the same time may be a better idea than looking for one at a time. This study reports a way to look for evidence of past viral encounter by looking for antibodies in the brain-bathing fluid, the cerebrospinal fluid. This study found that about 80% had encountered at least one of four viruses compared to no healthy individuals. However we know that MS is associated with a leaky barrier that fails to stop white blood cells, including antibody producing cells, and antibody from entering the brain, so could that account for the elevated level of viral-specific antibody being detected in the brain or is it really disease related and what about Epstein Barr Virus.

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  • That's amazing, when you can say that none of the healthy controls had any those 4 common viruses in their CSF compared to 80% MSer's. Most people get or are vaccinated against measles, german measles and chickenpox when children. If you've got a leaky BBB is this caused by the disease or is it physiological and possibly hereditary? Are these antibodies hanging around in the CNS for years, waiting to react with EBV when it enters? What about HERV's?

  • When I was a baby I went into convulsions I think a few days after I received a measles vaccine. The doctors at the time felt the two events were most likely related.

    When I was first diagnosed, my mom asked, "Did you tell your doctor about the measles vaccine?" Actually I had, because I have so few medical issues aside from MS that when asked if I have any drug allergies I usually respond that as long as I'm not getting a measles vaccine we should be fine.

    This is the first time I felt it appropriate to bring it up just in case all the other MSers had a similar experience and that's the reason for MS.

  • As Beverley said, most people will have antibodies to measles, rubella & probably chicken pox too, as a result of getting either the vaccine or the disease.

    So the difference between MSers and non-MSers lies in whether these antibodies can be found in the CSF?

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