Serial Monitoring of Salivary EBV in Multiple Sclerosis v1.0
Research type
Research Study
Full title
Measurement of Epstein-Barr Viral Load in Saliva of Patients with Multiple Sclerosis
IRAS ID
179636
Contact name
Sally Burtles
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
0 years, 6 months, 1 days
Research summary
Epstein-Barr virus (EBV) is the agent responsible for glandular fever (infectious mononucleosis). Exposure to EBV is virtually 100% in patients diagnosed with Multiple Sclerosis (MS) and over 99% have persistently positive EBV specific immunoglobulins (an antibody called IgG) compared to about 95% healthy individuals. EBV is so strongly associated with MS that many believe it is the cause of the disease. It is not known how EBV acts to trigger or perhaps drive MS disease activity, but unlike any other proposed causative organism, it is the only virus that has been identified consistently in MS [Ascherio and Munger 2010;Thacker et al. 2006;Thacker, Mirzaei, and Ascherio2006]. Furthermore, EBV can be detected in blood and saliva [Hadinoto et al. 2008a; Hollsberg et al. 2005a] making it easy to measure
The level of EBV can be estimated by measuring the DNA or RNA level of this virus. EBNA-1 IgG is a persistent antibody against EBV found in MS. A correlation between elevated serum EBNA-1 IgG and gadolinium-enhancing (i.e. recent) inflamed patches on MRI scans has been observed by one group [Hadinoto, Shapiro, Greenough, Sullivan, Luzuriaga, and Thorley-Lawson2008a;van Noort, Baker, and Amor2012], thus supporting an association between EBV infection and MS disease activity.
In a landmark study, Gulley and Tang 2010 showed that elevated Epstein-Barr viral load is associated strongly with current or pending post-transplant lymphoproliferative disorder (PTLD) which is known to be caused by EBV. In high-risk patients, repeated testing permitted early clinical intervention to help prevent progression toward full-blown PTLD. This similarity with PTLD made us consider that MS relapses might be connected with a surge in EBV activity prior to onset of clinical symptoms. If we were able to identify an increase of EBV level in saliva or blood, this would alert the clinician to a forthcoming relapse and provide an opportunity to prevent it, say with high dose of steroids.
It is easier to measure EBV-DNA in saliva than blood. Also, blood levels to EBV are lower and require measurement of viral RNA, a process that is technically more demanding. For this reason we wish to pilot the salivary technique prior to a larger study.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
15/EE/0427
Date of REC Opinion
25 Jan 2016
REC opinion
Further Information Favourable Opinion