What is the difference between a belief and a hypothesis? #MSBlog #MSResearch
Does EBV cause MS? Join the debate. #MSBlog #MSResearch
"The study below found no differences in EBV viral loads in the spinal fluid and peripheral between MSers and controls. Does this mean EBV has nothing to do with MS? No it doesn't. The link between MS and EBV is based on epidemiological and not mechanistic studies. I note from discussion We have no idea how EBV causes, or is causally linked to MS. All we have is a series of hypotheses that need testing."
"The Trillo-Pazos hypothesis was suggested by a virologist I was working with 10 years ago; unfortunately she never quite got her methods to work well enough to disprove her hypothesis. However, her hypothesis is the closest hypothesis to my field hypothesis. The field hypothesis doesn't necessarily depend on the virus being EBV; it could be HERVs or another virus that is deficient and requires co-infection with EBV to be pathogenic. I like the field hypothesis as it would explain the Prineas early MS lesion (oligodendrocyte apoptosis) and is congruent with the Japanese macaque encephalomyelitis model, which is the closest spontaneous animal model we have to human MS. I agree that any hypothesis that involves EBV needs to be congruent with current knowledge and explain all our epidemiological observations. The fact that natalizumab works, or at least it does in the short-term, does not exclude the field hypothesis. The latter may require a robust immune response to cause disease; there are well established precedents for this in virology. Some viruses are only pathogenic in the presence of an immune response."
- EBV triggers autoimmunity in the periphery by upregulating alpha-B crystallin in B cells (van Noort hypothesis).
- EBV immortalises central antigen-presenting B cells and when this is coupled with poor cytotoxic CD8+ T cell response drives CNS autoimmunity (Pender hypothesis).
- EBV infected B-cells in the CNS triggers a cytotoxic CD8+ T-cell response that damages oligodendrocytes and axons (Aloisi hypothesis).
- EBV triggers CD4+ T-cell autoimmunity via molecular mimicry (Wucherpfennig-Lünemann-Martin hypothesis).
- EBV transactivates human endogenous retroviruses that cause MS (Perron hypothesis).
- EBV is one of many viruses that provides the secondary danger signal that stimulates autoimmune reactions within the CNS (Meier hypothesis).
- EBV results in dysregulated T-cell function (Mainstream hypothesis).
- A mutant EBV strain infects glial cells and neurones and triggers an anti-viral response (Trillo-Pazos hypothesis).
"Enough said; the bottom line is I have no idea how EBV causes MS. All we have is a long-list of hypotheses that need testing. The good news is that several are being currently tested. The ones I would like to test are:
- Would targeting EBV lytic infection with an anti-viral reduce MS disease activity?
- Would treating infectious mononucleosis to prevent an aberrant immune response to EBV reduce your risk of getting MS?
- Would vaccinating young children to prevent them getting EBV reduce their risk of getting MS?
- Would infecting young children with wild-type EBV, without them getting infectious mononucleosis, reduce their risk of getting MS?"
"What is the difference between a belief and a hypothesis? You can disprove a hypothesis but not a belief. Fortunately, I am not a believer, which according to Popper makes me a scientist."
Aims: What has EBV got to do with MS?
Methods: The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection.
Results: EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC) positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples.
Conclusions: Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.
Labels: EBV, hypotheses, Popper