A Novel Association Between Human Papillomavirus and Thyroid Eye Disease

[helvella]

For many years, a vast proportion of documents appear to say that Thyroid Eye Disease (TED) - also know under various other names such as Graves' Eye Disease or Graves' Ophthalmopathy - occurs in association with Graves' Disease - the disease which results in hyperthyroidism.

You can talk to doctors, specialist nurses, read documents from NHS and eye specialists, and almost always get that impression.

Very rarely do you see mention of the fact that it can, and does, occur in cases of Hashimoto's where the patient is definitively hypothyroid, and in people in which no thyroid disease has been been found - possibly never even suspected.

If this paper (which, at present needs to be treated cautiously as it is a pre-print) holds water, then there is a cascade of questions. I suggest some of the following:

If it is a hard association, then why is there also a tendency for TED to occur in those with Graves' disease? Does this lead us to wonder if HPV has a role in Graves' Disease?

Does HPV vaccination reduce the likelihood of suffering TED? Given the fairly widespread cover by HPV vaccines, especially in the younger population, this could be very important. Are we already seeing a reduction in TED in the age group who have widely received HPV vaccination?

(However, there is a large number of HPV variants and it will, of course, be necessary to consider whether they all have the same effects, or possibly just a few.)

Even if, in time, this is seen as something of a false dawn, I think it just might wake up research a bit.

A Novel Association Between Human Papillomavirus and Thyroid Eye Disease

Ishita Garg, Benjamin I Meyer, Ryan A Gallo, Sara T Wester, Daniel Pelaez

PMID: 38746201 PMCID: PMC11092719 DOI: 10.1101/2024.04.27.24306443

Abstract

Context: Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R).

Objective: To explore the potential involvement of viral infections in TED pathogenesis.

Methods: Using NCBI BLAST, we compared human TSHR and IGF-1R proteins to various viral proteomes, including Papillomaviridae , Paramyxoviridae , Herpesviridae , Enterovirus , Polyomaviridae , and Rhabdoviridae . Enzyme-linked immunoassays (ELISAs) were performed on orbital adipose tissue samples from 22 TED patients and controls to quantify antiviral antibody titers. Demographics and clinical data were reviewed.

Results: Homology analysis revealed conserved motifs between TSHR and IGF-1R with several viral proteins, particularly the human papillomavirus 18 (HPV18) L1 capsid protein. Basic demographic and clinical information between the cohorts were comparable. ELISAs showed statistically significant differences in the average HPV18 L1 IgG normalized optical density levels among tissues of control ( M = 0.9387, SD = 0.3548), chronic TED ( M = 2.305, SD = 1.064), and active acute TED ( M = 4.087, SD = 2.034) patients. These elevated HPV18 L1 IgG titers did not statistically correlate with TSH, T4, or TSI levels, and were elevated in TED patients irrespective of treatment with teprotumumab, indicating a direct immunological response to HPV.

Conclusions: This study presents the first molecular evidence linking HPV and TED, highlighting molecular mimicry between HPV capsid protein and key autoimmunity targets in TED. This suggests an immunological link contributing to TED's pathogenesis, opening new avenues for understanding and managing the disease.

pubmed.ncbi.nlm.nih.gov/387...

Full text currently accessible here:

medrxiv.org/content/10.1101...

I must re-emphasise that this is a pre-print and is liable to being edited, or retracted before publication, and links might not work into the future.

[Buddy195 Administrator]

Interesting links helvella. I asked both my endo and TED specialist ophthalmologist why they thought I developed TED alongside Hashimotos. Endo still adamant I had Graves first (which he believes burnt itself out), although ophthalmologist says in recent years he has seen more people with TED who have Hashimotos or are euthyroid.

[helvella Administrator Thyroid UK in reply to Buddy195]

So far as I know, no-one who claims that TED is in some way caused by GD has ever explained, produced a reasonable hypothesis, as to why so many don't end up with TED.

Not saying such a possibility doesn't exist, but in order to apply it to real people, it needs a bit more than a hand waving and 'because I say it'.

I'm also very sceptical of this idea of Graves burning itself out. The very words - 'burnt itself out' - make it sound like an old-fashioned electric fuse, or an old tungsten filament lamp. Something has overloaded a circuit and the fuse wire has melted. I find it difficult to see a biological equivalent.

Happy to believe things can fade away. That is a common enough thing in biology.

[nooneimportant in reply to helvella]

This is really interesting 🤔 I had a string of trauma and then tested positive for HPV shortly before my graves diagnosis two years ago …. HPV then went dormant (whatever they call it) then came the itchy eyes (thought it was onset of hayever) poly morphic light eruption (always told it was heat rash even though it erupted in light rather than heat) then the graves diagnosis. Ive noticed itchy eyes and the Poly morphic light eruption isn’t erupting as much this year and I think graves is now going into remission (but don’t want to curse it and getting no endo input atm so can’t be sure) … before reading this I did wonder if all this might be somehow related 🤷‍♀️🙃 but unlikely to get answers from nhs 😂