Whilst the crusade for EBV and MS gains momementum, the question I posed just before Christmas was “Is there anything special about EBV and MS or will EBV associate with other conditions?” Because if it does, then the approaches to deal with EBV to treat MS may not be so simple. Importantly, if it is is important the question is when is it important? Because if it is the cause, is it important before MS shows itself then treatments need to be focused there. We have seen a lot of vitamin D trials in MS and other conditions that really didn’t go anywhere, when the the biology was arguing for a more major influence much earlier. I think we need the right trials not the easy trials.
In this study they go hunting for evidence of responses to viruses in MS, healthy people and people with another neurological condition (TSP) known to be related to a known viral infection. They use a tool to find responses to viruses in the blood and the spinal fluid and they can find evidence for responses for the known virus type that causes the non-MS neurological disease (Tropical Spastic paraparesis). So the technology works for virus hunting. This virus is not a part of the MS response, but when it comes to MS, yes there maybe be some elevated response to EBV in MS compared to the healthy individuals, however they elevated find responses to EBV in the other conditions There is no single MS viral response and there is nothing special in the type of responses in MS that can’t be found in the other neurological conditions. However, there is a signature of viral infections.
This warns us , if you do science when you do not look for alternative answers, you are only going to see the reality you want to see. So you are doing science you want to prove. You should be trying to disprove your idea and if you do…..get a new idea. However, this is seldom done. My idea that EBV can be important in conditions outside of MS remains intact. Next experiment anyone.
In this study they look at responses to hundreds of viruses and see responses to multiple viruses. Now it doesn’t say that EBV is not the cause of MS, but it provides no evidence that MS is specific to EBV infection.
Enose-Akahata Y, Wang L, Almsned F, Johnson KR, Mina Y, Ohayon J, Wang XW, Jacobson S. The repertoire of CSF antiviral antibodies in patients with neuroinflammatory diseases. Sci Adv. 2023; 9(1):eabq6978. Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Although various viruses have been proposed to contribute to MS pathology, the aetiology of MS remains unknown. Since intrathecal antibody synthesis is well documented in chronic viral infection and neuroinflammatory diseases, we hypothesized whether the patterns of antigen-specific antibody responses associated with various viral exposures may define patients with CNS chronic immune dysregulation. The pan-viral antibody profiling in cerebrospinal fluid (CSF) and serum of patients with MS showed significant differences from those in healthy volunteers and a pattern of antibody responses against multiple viruses, including the previously identified Epstein-Barr virus. These findings demonstrate that virus-specific antibody signatures might be able to reflect disease-associated inflammatory milieu in CSF of subjects with neuroinflammatory diseases.
They say “To date, a number of infectious viruses, including measles, mumps, Epstein-Barr virus (EBV), human herpesvirus, and other ubiquitous human herpesviruses, have been proposed to contribute to MS pathology, although not one virus has been definitively shown to be the causative agent . In particular, a link between EBV and MS has long been suspected, and recently, this association has again re-emerged based on recent reports demonstrating increased EBV-specific antibodies in serum of patients with MS”.
They say “…it is unclear whether antibody responses against EBV are uniquely elevated in MS and what is the extent of EBV reactivity in the CSF of patients with MS?……In addition, it has been suggested that virus-specific immune responses may cross-react with self-antigens (molecular mimicry), thus contributing to the pathophysiology of the disease”.
We here hypothesize that if environmental factors including virus infections and immune reactivation against viruses play a role as “triggers” in MS, then antibody signatures against such viral exposures may be defined that represent immunological signatures in patients with MS.
To identify virus-specific antibody signatures, they tested spinal fluid and paired blood (serum) of MS patients and healthy normal volunteers (HVs) using VirScan, an established platform for the profiling of the entire known human virome (viruses present in humans) that detects response to 206 known human pathogenic viruses.
First they went hunting for viruses in Tropical spastic paraparesis and they found the virus subgroup (HTLV1) known to be a causative agent and they didn’t find it in MS. Then they hunted in MS and didn’t find any antibody response against any single virus specific for MS that couldnt be found in controls and whilst there was increased responses to EBV in MS, these could be found in other people too.
Are multiple viruses triggering multiple autoimmunities? I don’t think you have to evoke this view
CoI: None relevant
Disclaimer: These are the views of the author