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I invest a lot of effort into my research.  In order to more effectively treat MS, we need to better understand what causes it.  Here is a summary of some of my recent research.  I'd like to say a big "Thank you" to those of you who participate in these studies, since none of this would be possible without your generosity.  

Epstein-Barr virus and MS
One of my interests is the role of Epstein-Barr virus (EBV) in causing MS.  Infection with this common virus has been linked to MS, but it is not clear how the virus might cause the disease.  We have several projects focused on various aspects of Epstein-Barr virus and MS, some of which are completed and published. 
Work in progress
Does EBV cause MS activity?  We are testing whether EBV reactivation is what causes disease activity in MS.  We measure changes in the amount of EBV in the blood and changes in the immune response to EBV, and compare that to disease activity on MRI.  This study requires a lot of dedication from the participants, since we have blood draws every 2 weeks and MRI scans every 4 weeks for a total of 16 weeks.  We are aiming to recruit 20 subjects for this study in 2012 and 2013.  We are looking for people with recently diagnosed MS and active lesions on a recent MRI scan to participate in this study. 
Completed studies
Is the antibody response to EBV altered in MS?  Antibodies or immunoglobulins are proteins made by the B cells of the immune system that specifically bind to a certain virus, bacteria, or protein.  They are important for controlling infections, and have a lot of different functions.  We measured several different antibodies to EBV in MS and controls.  We found that antibodies to the EBV nuclear antigen are increased in MS, as have several other investigators.  We also looked at neutralizing antibodies, which bind to EBV and keep it from infecting new cells.  These weren't any different in MS.   
Is the immune response to EBV defective in MS?  This was a more complicated study.  We first infected blood cells with EBV, and grew them in culture until we had a lot of them.  Then we got a second blood sample from the same person, and measured how the different types of cells react against the virus.  The CD8 cells didn't seem to be as effective at killing virus-infected cells in MS, but other aspects of the immune response were intact.  The differences between the MS group and the controls were suggestive, but not significant. 
Do people with MS have a worse infection with EBV?  We measured how much virus was present in the blood of people with MS and a group of matched controls.  The amount of virus in the blood varies a lot in both MS and controls, but there wasn't any difference in the two.  We did find that EBV in the blood tended to increase during relapses, and especially before relapses.  This is consistent with the idea that maybe reactivation of EBV provokes MS relapses. 
Lindsey JW, Hatfield LM, Crawford MP, Patel S. Quantitative PCR for Epstein-Barr virus DNA and RNA in multiple sclerosis. Mult Scler2009 Feb;15(2):153-8.
Do people with MS have a different strain of EBV?  After the initial infection, EBV stays in a latent state in the blood cells, and you can determine what strain of virus is present in the blood.  We did this in a group of people and found that there was no difference in virus strain in MS. 
Lindsey JW, Patel S, Zou J. Epstein-Barr virus genotypes in multiple sclerosis. Acta Neurol Scand2008 Feb;117(2):141-4.

Other studies in progress
What changes occur in MS relapse?  We don't really know what causes MS relapses, nor do we know what is going on in the immune system that causes a relapse.  We have used a new technology called micoarrays to investigate this question.  Essentially, microarrays allow you to measure a bunch of different things at the same time.  We are using them to measure the amounts of RNA for about 22,000 different proteins in the blood, and measuring which ones are increased or decreased in relapses.  We have some interesting resutls, which we are in the process of analyzing. 
What is the target of the immune attack in MS?  One of the features of MS which we use as a diagnostic test is that there are oligoclonal bands in the spinal fluid.  Basically this means there is a specific immune response going on inside the brain, but nobody knows what protein this response is attacking.  We are using spinal fluid that we have collected over the last several years to try to figure out the target of these antibodies.  We are getting some interesting results, but they are still at a very preliminary stage.  

J. William Lindsey, MD
University of Texas Multiple Sclerosis Research Group
Houston, Texas

copyright 2007-2017 John William Lindsey