Permission to repost by Prof. G Risk factors for developing MS: the case for EBV gets stronger. "The study below was a massive effort by Dr Jens Kuhle, who was generously funded by an ECTRIMS fellowship to do this work. Well done Jens!" "This work confirms many findings, but also provides new information on an association between oligoclonal bands and raised antibody titres to EBV infection. The whole reason for doing this study was to see if there was a link between EBV infection and OCBs. This study hints at EBV being linked to OCBs. How? Maybe EBV drives the B-cell response in MS. Unfortunately, too few CISers were EBV negative in this study to test to see of EBV-ve CISers were likely to be OCB-ve; even those CISer who were 'EBV-negative' using the EBNA-1 antibody screen were positive with more sensitive assays. This confirms that if you have CIS and are at risk of developing clinically definite MS you are virtually assured of being EBV positive. The corollary to this is that if you are EBV negative you don't develop CIS or MS. The Billion Dollar question is how do we keep the population EBV negative and is it wise to do so? An EBV vaccination strategy may work, but what will the consequences of getting rid of EBV in the wider population? EBV is part of our metagenome and it is one of the most co-evolved human viruses. This would imply that it must be doing something favourable at a population level for evolution to have moulded such a close relationship between humans and EBV. This is why we are focusing our attention on infectious mononucleosis (IM) which increases your risk of getting MS by a factor of two (2X). How does IM trigger the MS causal pathway? If we prevented and or treated IM would we reduce the risk of you getting MS? These are all very important questions for the future. Someone needs to answer them. If we don't the next generation of CISers and MSers will ask why we didn't act given the information we currently have. Despite the firm evidence that EBV plays a role in MS we still get very negative reviews when we submit grant applications to study this further. We must be doing something wrong." Comments and Posting By Gavin Giovannoni Epub: Kuhle et al. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study. Mult Scler. 2015 Feb. pii: 1352458514568827. BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. CoI: This work was done by TeamG who are also authors on the paper.