A potential antigenic mimicry between viral and human proteins linking (ME/CFS) with autoimmunity:The case of HPV immunization - Phelan Feb 2020

A potential antigenic mimicry between viral and human proteins linking Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with autoimmunity: The case of HPV immunization

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https://www.sciencedirect.com/science/article/abs/pii/S1568997220300355


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(no abstract as such)
https://sci-hub.tw/10.1016/j.autrev.2020.102487

 

https://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/antigenic-mimicry

"Antigenic mimicry is the sharing of antigenic sites between microorganisms and mammalian tissue. An immune response can be directed both at the microorganism and at the host site that shares the antigenic determinant. This autoimmune response due to antigenic mimicry is known to be a crucial factor in the development of certain ailments in humans...."

 

Can'o'worms.

This paper is predicated on speculative computation based guesswork about the possibility that HPV vaccine proteins could mimic human intracellular proteins and trigger autoimmune disease including ME via an hypothetical mechanism involving Treg suppression of autoimmunity as mooted in the Nacul paper a while ago.

The speculation goes way beyond the actual work carried out and additional discussion of vaccine adjuvants and macrophagic myofasciitis (MMF) steps deeper into the medical-political-commercial minefield surrounding what the WHO currently regard as unproven suspicions about vaccination.

WHO Global Vaccine Safety : Macrophagic myofasciitis and aluminium-containing vaccines.
https://www.who.int/vaccine_safety/committee/reports/october_1999/en/

I feel the consideration of adjuvants in relation to mimicry theory in this paper is a non sequitur in relation to the title. It seems to me this early draft of this paper is being used to advertise a grievance and its publication is perhaps an attempt to raise awareness of the adjuvant controversy, apparently based on Romain K Gharardi's decision to address ME CFS in his own paper as part of what appears to be a long running campaign against aluminium in vaccination adjuvants, which has its opponents. I would remind readers of the controversy over the autism/Thimerosal theory and the harmful consequences of these ideas which are now considered debunked. This paper does not consider epitopic mimicry at all.

https://www.researchgate.net/public...ersistency_and_diffusion_in_the_immune_system

Gharardi equates ME/CFS due to EBV (a virus) and Coxiella burnetti (intracellular bacterium causing Q fever) and "Borelia burddorferi", (a blood born bacterium which causes Lyme disease), with each other and with ME/CFS due to aluminium particles in the muscles of vaccination recipients causing MMF without any empirical basis for doing so.

I have seen papers containing empirical evidence interpreted as meaning EBV produces TH2 shift and Lyme TH1 which suggests to me these have distinct etiologies and are likely to be different subtypes of CFS, or possibly different conditions entirely.
https://www.s4me.info/threads/comparison-of-diagnostic-criteria-discussion-thread.7508/#post-206312

The Gharardi paper offers no evidence that these conditions are related apart from subjective matching of loose CFS criteria e.g. to the best of my knowledge it is not known whether they are all marked by TGF-beta increase for example, which would at least indicate they were related subtypes which could all be candidates for testing the Treg / mimicry / Tcell suppression theory if it was the case, so I feel lumping them all together is not meticulous and is probably a class error and regard this as speculation which as yet provides no basis for linking alleged MMF induced CFS to the mimicry theory.

So the Sepúlveda paper is speculation about speculation, a shot in the dark and not empirical science.

While speculation is not a crime, I also feel that linking ME research to MMF and unsubstantiated claims against adjuvants is likely to harm the reputation of ME research in the medical establishment and so constitutes a risk without a valid justification. While I have felt for a while now that seeking funds for credible research couldn't get any more frustrating, now I am not so sure.

As an ME patient its always interesting to know what researchers are thinking, but I feel that through this paper, we, the vulnerable ME community, are being played and used for someone else's crusade and I don't like it, I dont think we deserve that. If they really want to publish this work in a useful way for ME and mimicry theory research, my feeling is they would do better to constrain the discussion to the discoveries of the computation, lay out the possibilities for lab testing the hypothetical topological predictions in vitro (since sequence homology does not an epitope make due to secondary, tertiary and quaternary structure, so this must be verified in vitro) and avoid theorising beyond the scope of the discoveries and mimicry the title addresses.

 

I came across an example today of how limited computer modelling of sequence affinity is, therefore how incomplete a foundation it is for predicting mimic epitopes.

The discussion of SARS in relation to other viruses in "virology blog" founded by Vincent Racaniello and featuring David Tuller's articles on ethics in ME research, describes how a six amino acid sequence in SARS with high affinity for a particular epitope (ACE2) shared only one amino acid with another such sequence in its closest relative, a bat virus, which binds a bat epitope equivalent. Five of the amino acids were different and computer modelling was not able to predict the affinity.

Computer modelling will hopefully learn from this and improve but this shows how reality is more complex than computer models and how evolution proceeds by iterations selected by real world outcomes which computer models cannot always predict. While the blog uses this to make the point that the virus could not have been engineered deliberately and could only have arisen through natural selection, there is a more general lesson here for the search for mimicry. Computational analysis may be a useful tool which shows us more than we once knew but it is not infallible nor complete. Which reinforces the point that any predictions have to be tested in vitro before they can be considered real and searches for binding affinity in the study of mimicry should not be left to computer modelling and should also be carried out using real world biochemical techniques (which supports points made the final paragraph of my post above so I thought it worth blogging the blog ).

http://www.virology.ws/2020/02/20/pangolins-and-the-origin-of-sars-cov-2-coronavirus/

(Edit to correct a potentially misleading summary in para 2 which made it sound like the bat epitope was the same as the human epitope.)