Thursday, 26 September 2013

EBV in Childhood MS

More data to support EBV as being involved in the causal pathway of MS. #MSBlog #MSResearch

"This study fingers EBV again, only this time in children MSers. Children with MS are more likely to be seropositive for EBV and shed EBV in  their saliva. Why? Is it because they have a more virulent strain of the virus? This looks unlikely as no specific EBV variant was associated with MS. You need to realise that EBV is not one virus but a family of viruses. Could it be that there is something faulty in the immune systems of these children allowing the virus to replicate unchecked? I suspect this is the most likely explanation. Unfortunately, we don't know what is wrong with the immune systems of MSers that allows EBV to be more active."

"You will note that not all childhood-onset MSers are positive for EBV, which is a strong argument against the virus causing the disease. I agree that this is one hole in our EBV  theory. IF EBV causes MS there are two possible explanations for this observation. Firstly, not all these are EBV negative; the assays used to test for antibodies against EBV are not 100% specific. Secondly, these MSers may not have 'classic MS'. It is more difficult to make a diagnosis of MS in childhood due to more MS mimics and other non-MS like demyelinating diseases presenting as MS. The only way to assess this is to follow the EBV negative MSers to see if they behave like adult-onset disease in the future or turnout to have anothe disease."
"I am still firmly in the camp that believes EBV is thc cause of MS and may be involved as a driver of the ongoing inflammatory activity. To test these hypotheses we need to EBV vaccine trials to prevent children getting EBV or at least infectious mononucleosis and we need to do clinical trials of drugs that target EBV replication and reactivation in MSers with active MS. Why active MS? We need to have an outcome to assess whether or not an antiviral drug is active in a relatively short period of time. This is why we use relapses and MRI activity as an outcome measure."


OBJECTIVE: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with MS.

METHODS: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric MSers and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry.

RESULTS: Nineteen of the 22 (86.4%) children MSers were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive MSers compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in MSers and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus-1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in MSers; however, no specific EBV genetic variant was preferentially associated with MS.

CONCLUSION: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV.

6 comments:

  1. You're feeling sorry for yourself, then you read about CHILDREN with MS!

    All of a sudden I realise than getting to 31 years old oblivious to this disease and to 38 before a wheelchair with my name on it beckoned, could've been so much worse.

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  2. Does the chance of getting MS increase if someone gets full blown Mono from EBV not just being a carrier of the virus? I was hospitalized when I was 19 with a very severe case of mono and was diagnosed last year at 45 with MS, although I believe my first attack was at 37.

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    1. Re infectious mono

      Yes, IM is the real risk factor. It increases your chances of getting MS by over 2.

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  3. If EBV negative children get MS shouldn't you start rethinking the Charcot project?

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    Replies
    1. Re: "If EBV negative children get MS shouldn't you start rethinking the Charcot project?"

      Not at all; not everyone who is diagnosed with MS has MS. In adults 1 in 20 MSers are misdiagnosed; in children the misdiagnosis rate is even higher. Also the tests that are used for diagnosing EBV give a false negative rate of between 4-6%. Nothing is black-and-white. This is why the philosophy of science and medicine is so important. How do you define a disease? What is the sensitivity and specificity of diagnostic criteria or a laboratory test?

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  4. Why is IM a real risk factor? Is a titre of EBV in the blood higher permanently if a person has had IM as compared to someone who has tested positive to EBV but has not had IM?

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