Negative Association of [GWI] Symptomatology with Predicted Binding Affinity of Anthrax Vaccine Antigen to [HLA II molecules], 2025, James et al

Seems sensible to me within this study, but isn't the whole idea based on a study with far less participants were they looked at how a subset of genes differed in a GWI(+) and GWI(-) cohort?

 

They aren't.

I don't these GWAS type problems are relevant here. We have a small cluster of polymorphic loci with known functional differences and the study relates symptoms to those specific functions. Being on the internet is highly unlikely be linked to MHC-II. We are not dealing with a situation where we do not know what genes we are looking for.

 

Then that example can clearly be thrown out of the window.

 

Yeah, but that's basically what most pilot studies are, and they're followed up by a larger study with more power.

I understand the method they used here and it makes sense to me for testing their hypothesis. (Notwithstanding any issues with the hypothesis itself that Jonathan mentioned.)

In the smaller study, as far as I can tell, they used a quite different method for the HLA part where I don't think it's as straightforward to draw the same conclusion, though I've only skimmed that one. But at least this more robust study seems to agree with the proposed association from the earlier one.

 

Isn't it possible the toxin migrates to somewhere like the brain and maybe it takes time to eat away at the myelin or something? (Maybe something more difficult to test for)

Can you explain this part? I'm not really sure what you're saying.

 

Jonathan made a good point in another thread:

Any association involving HLA might just be related to how the body deals with an infection. We already know that more severe infection increases the risk of long COVID - maybe ME/CFS too - so what we see in HLA in long COVID or ME/CFS might just be that these alleles cause more severe acute infection. @Jonathan Edwards, is that about right, and do you have any ideas for how HLA might actually be more relevant to an ME/CFS "disease process"?

 

That seems to me exceedingly unlikely. As far as I know anthrax toxins kill people pretty rapidly. If those people are given antibiotics and the infection is dealt with they recover.
Bacterial toxins tend to be proteins that bind to cells receptors or metabolic organelles and are likely to be degraded as the cell dies more or less immediately.

If the toxin is around and dangerous for the first 24 hours then the only antibodies around at that time will be ones already made in advance - and these are largely broad-specificity IgM antibodies.

It is worth remembering that the main reason we make antibodies is to stop getting an infection twice. Building up enough antibody to eradicate an infection takes more than a week and most fatal infections kill earlier than that. Women also make antibodies to protect their children in the first three months of life when they have very few of their own.

The other important point is that the immune system can only make usefully specific antibody to an antigen if it has already made some rough and ready IgM antibody to pick up the antigen and show it to B cells in the first place. High quality IgG antibody comes from cells that originally made IgM and went through a series of selection and mutation steps to make the antibody more specific.

 

Roughly but some HLA alleles are good for reacting to one infection and others good for other infections - at least that is the standard theory, with at least some evidence. Interestingly, though, some HLA alleles may just be a bit more 'aggressive'. HLA-B27 seems to protect against various infections but it is also the main risk factor for the auto0inflammatory disease ankylosing spondylitis.