Reacción a "Reactions: specific antibodies found in blood samples from patients years before they develop multiple sclerosis"

This study is the result of research conducted over many years by a group of researchers at the University of San Francisco in California (UCSF) and the Chan Zuckerberg Biotechnology Research Center (Biohub) in the same city. The initial purpose was to discover causative agents of multiple sclerosis (MS), a chronic neurological disease affecting the central nervous system (CNS, which includes the brain, spinal cord and optic nerves) that it is presumed to be immune-mediated (autoimmune). MS causes demyelination and axonal damage, resulting in a wide variety of symptoms.   

To do this, they used a complex biological technology ('phage expression libraries') that allowed them to study more than 10,000 proteins present in the human body, to detect which of the antibodies present in the blood of these people with MS  -or groups of antibodies- were the ones damaging or attacking structures in their CNS and producing the disease. — Thus behaving as autoantibodies. —  

One of the main strengths of this study is that the blood/serum samples from these subjects came from the US department of defence serum repository, which stores samples from more than 10 million US military personnel. Of these, 250 subjects subsequently developed MS over the years. And what could be seen is that 10 % of these people with MS had and shared a specific set or group of antibodies in their blood, already years before they developed the disease. These antibodies, moreover, were very similar to those that develop in the course of infections caused by micro-organisms that very frequently affect humans, including the Epstein Barr virus (EBV), which has been linked in many previous studies to MS.   

It is again clear from this study that the immune system of people with MS mistakes the proteins of this virus for those of their own CNS and attacks them, leading to the symptoms of the disease. This is because EBV - and possibly other viruses as well - contain protein sequences similar to some proteins present in the CNS.  

For these kinds of conclusions, it is not possible to conduct randomised studies (which are the highest level of evidence of health outcomes possible), so what are known as 'natural experiments' - longitudinal studies of incident cases of MS - are conducted. Moreover, these data were confirmed in another cohort of patients and there is biological plausibility that they are credible. It was also possible to rule out reverse causality (in this case, it was deemed highly unlikely that it was the MS what predisposes individuals with MS to have an EBV infection).  

This study fits well with the results of previous studies. Firstly, there is a pre-symptomatic or preclinical period of the disease that lasts several years. During this phase, the patient does not  have yet the typical symptoms of MS, but has other non-specific, prodromal, symptoms, in which an inflammatory process within the CNS may already be developing. However, very few patients are diagnosed with the disease at these stages. On the other hand, it helps to consolidate the importance of EBV in the development of MS. Two years ago, another important study was published -also in the same cohort of US servicemen-, that showed a MS risk increase of 32-fold after EBV infection, but not after an infection of other viruses that are transmitted in a similar way, such as cytomegalovirus. It is currently the most important and well-established risk factor.  

The most important consequence of all this is that, by studying this immunological fingerprint, it might be possible to identify subjects at risk of developing MS in the coming years and, thus, start disease-modifying treatments as early as possible and implement all the measures aimed at preventing the accumulation of disability. On the other hand, and preventively, the development of an effective vaccine against EBV could potentially prevent this disease if applied before the subject has been infected by the virus. In addition, the results of this research open new paths to improve health outcomes for MS patients.