If you cannot explain the outliers you do not understand the disease. There are more ways to mimic the human proteome or induce autoimmunity than just Epstein-Barr virus - but those outliers existing does not mean the molecular mimicry hypothesis can be dismissed out of hand.
Yes! The question IS very much "why some people end up with the bad autoantibodies and others don’t."
My comment was about how you can’t ignore the EBV naive lupus cases when trying to explain how lupus works.
I am surprised to see this being suggested on here. I thought we not only lacked evidence for vaccines causing autism but had good evidence against it.
That reply was to JE not you - he is dismissing the concept of molecular mimicry by claiming there is no evidence for it - I am in vehement disagreement with his dismissal - although I agree even star cases supporting it have their own deficiencies and caveats.
I too doubt vaccines are the primary cause of autism - I think the case is far stronger for in utero issues (like an autoantibody) transferred from mom to fetus skewing development.
Viruses do not cause new types of antibodies to be created, do they? They just amp up the production of those that have already passed multiple checkpoints against autoimmunity.
You’d still need to explain which parts of «immunity» that’s fallible, and how those flaws allows for the survival of autoantibodies at a scale large enough, with high enough affinity, to cause disease.
Which processes?
A change in the form of the cells in the body due to external factors might in theory be a way to get around the issue with checkpoints against autoantibodies. But the change would have to be quite consistent across individuals for it to generate the same kind of disease. And the changes would have to happen at a large enough scale to cause disease.
I misunderstood because the reply was in a comment that responded to my comment.
It effectively makes EBV redundant, so you’d have to explain either how there are two different processes that can cause lupus, or how EBV supercharges the lupus process that can still occur without EBV.
I appreciate the engagement as well!
Is there good evidence such “idiopathic” cases exist? Most parents are not able to detect signs of autism that early. In fact, that is the norm except perhaps in fairly severe presentations. That’s very different from autism actually not being present from birth.
pubmed.ncbi.nlm.nih.gov
I’m honestly lost in the epidemiology of this field. Diagnostic criteria do change; how much rates are up vs historical. But lots of immune things are up vs historical and if autism has immune link (assume it does) it going up now would fit other global trends. I have a client at NIMH that recently ran PANDAS samples with us on HuProt but cohort was blinded to me so do not know the result or how that went. About to do my own maternal study with women known to give birth to kids diagnosed early by hearing test and look more at viral/bacterial exposures correlating via a new “exposome” VirScan phipseq (which I guess I designed - expecting that data within the week). I’m not just debating out of the air I’m actively trying to test these hypotheses …!
It’s not genetics alone. So what would cause this pruning issue ? Part of why I’m so obsessed with autoabs as a direction. Maternal antibody to fetus (remaining in circulation first months of life for baby too) could block neuronal growth factors that do such things.On autism I read a "synaptic pruning" theory that suggested everyone builds then prunes synapses during brain development, but in autism the ones that get pruned off are different.
E.g. many more of the social learning neurons get pruned and many fewer of the neurons related to say, numbers etc.
I find this to be an intuitive model for the phenotype. There's not a lot of evidence for it yet though.
The over-pruning hypothesis of autism - PubMed
This article outlines the over-pruning hypothesis of autism. The hypothesis originates in a neurocomputational model of the regressive sub-type (Thomas, Knowland & Karmiloff-Smith, 2011a, 2011b). Here we develop a more general version of the over-pruning hypothesis to address heterogeneity in th …
"The proposed atypical mechanism involves overly aggressive synaptic pruning in infancy and early childhood, an exaggeration of a normal phase of brain development. We show how the hypothesis generates novel predictions that differ from existing theories of ASD including that (1) the first few months of development in ASD will be indistinguishable from typical, and (2) the earliest atypicalities in ASD will be sensory and motor rather than social."
I don't think we know what controls synaptic pruning but I imagine a virus or autoantibody is not ruled out as a contributor to it going haywire.
It is, but that’s quite different from the idea that there are kids who are simply not autistic at all before that point, and something (like a vaccine) happens that makes them autistic.
I respect that. I just don’t think the vaccine angle specifically is viable unless you can explain how the connection has been missed repeatedly. You’re saying there’s a plausible mechanism for vaccines to cause autism, but the existence of a mechanism isn’t enough if there is research showing no numerical relationship.
Literally *nobody* knows the mechanism of autism or even what it entirely is. There are no diagnostic biomarkers. No molecular classes. It’s all diagnosed on vibes, questionnaires, pain responses with lots of vague associative and descriptive studies of patterns that occur without clear cause. Until we know more *everything* is on the table. My point is not that I think vaccines cause autism. My point is that I think it’s plausible autoantibodies are involved in what causes autism. And that the way I know how to measure autoantibodies is relatively new and has not really ever been used to check for whether vaccines change them, etc. Thus, a gap in human knowledge directly at this interface I happen to specialize in. Doesn’t mean the answer is there - just unchecked and IMHO more than worth checking as much as everyone claims to already know the answer as to what does or doesn’t cause it. Every scientist I’ve ever brought this up to looks at me like some sort of demon who has broached a forbidden taboo - and that I don’t like. Many are terribly uncurious creatures.
