Why was this information guide developed?

This content is about an unusual medical event discovered only in recent years that is most fitting for the colloquial but non-medical term of “turbo cancers”, a phenomenon often anecdotally described to be observed during the pandemic (although still without corroborating scientific data).

The reason why I think this is an important guide to produce is strictly because of one common link between turbo cancers and the mRNA vaccinated individuals who now make up the majority of the global population: IgG4 antibodies.

In a nutshell, this guide attempts to explain the molecular biology of turbo cancers, their link to IgG4 antibodies, and provides potential warnings to mRNA vaccinated individuals on how to monitor their situation in case the unusual and surprising side effect of the development of IgG4 antibodies observed in the vast majority of mRNA vaccinated individuals turns out to be a health risk.

Currently, we do not know if this phenomenon of build up of IgG4 antibodies targeting the spike protein in the mRNA vaccinated is a health risk or is either benign or even perhaps protective in nature.

We provide this guide in case the increase of IgG4 antibodies in mRNA vaccinated individuals could be a predisposing risk to cancer development.

In the tragic event that elevated IgG4 antibodies in mRNA vaccinated is a predisposing cancer risk, we need to consider any potential protective measures.

The take home message is that IgG4 antibodies in a cancer environment could aid cancer development. In a further unusual circumstance that the same cancer environment is also rich in glutathione, such a situation could lead to the development of turbo cancers. That is what very limited scientific knowledge currently suggests.

What are turbo cancers?

This term does not exist in medicine at the moment, while widely used colloquially by the public. It refers to unusual very rapidly growing and deadly cancers. In medical terms, the closest described concept that involves IgG4 antibodies is what is referred to as hyperprogressive disease.

Hyperprogressive disease is a state where a cancer patient who was treated with anti-cancer medication (referred to as immune checkpoint inhibitors which are IgG4 antibodies targeting specific molecules of interest) experiences an abnormal and dramatic increase in cancer development (usually with worsening outcomes) instead of reduction or stabilization of their cancer.

Because this is a very recently documented phenomenon, little science has been published thus far explaining the potential molecular mechanisms behind this unusual phenomenon.

However, it is now becoming accepted that hyperprogressive disease (turbo cancers) is caused by the anti-cancer medication itself in a subset of cancer patients. It is now further believed that it is the fact that the anti-cancer medication is an antibody of the IgG4 subtype that is responsible for this. Until hyperprogressive disease was documented, it was not understood that IgG4 antibodies could be dangerous to enhancing cancer development risk in some people. It now appears that it is the IgG4 antibody structure that imposes this increased risk.

How are mRNA vaccinated tied to this?

There is now an increasing body of evidence that nearly all mRNA vaccinated individuals are switching their antibody production against the spike protein towards the IgG4 subtype unless certain specific events took place prior to mRNA vaccination. At the moment, these appear to be either certain types of immunosuppression medication or natural infection with SARS-CoV-2 virus. Of the different vaccines studied so far for this effect, the rise in anti-spike IgG4 levels is only observed in mRNA vaccinated individuals, either the Pfizer or Moderna shots.

It is not yet clear how long the protection from IgG4 production lasts with subsequent boosting with mRNA shots but the protection appears to exist in most of those who only had 2 mRNA shots.

What is also not clear is whether the increase of IgG4 antibodies targeting the spike protein significantly impacts the total levels of circulating IgG4 antibodies and whether this is even a dangerous event for cancer risk development.

If total circulating IgG4 levels in mRNA vaccinated individuals are not affected, this might not even be a risk factor to such people, and perhaps such antibodies might even play an important protective role instead.

However, since at the moment we do not clearly know what is the answer, I recommend taking a precautionary approach.

Finally, what is also not fully clear yet is how long the elevated IgG4 antibodies in mRNA vaccinated persist, but currently, limited evidence suggests it could last for many months post last mRNA vaccine shot. Furthermore, evidence is also mounting to suggest that additional shots or breakthrough infection can either further boost or maintain the already high levels of IgG4 antibodies in the circulation.

What are the risks?

The primary risk is elevated IgG4 antibodies in a cancer microenvironment. This means that at least two criteria have to happen at the same time:

• Presence of cancer cells
• IgG4 antibodies (irrelevant of what these antibodies target) being able to enter cancer surroundings from blood vessels. This suggests that such a situation would need elevated blood concentrations of IgG4

The degree of enhanced cancer risk in such a situation is not understood because the concept that IgG4 antibodies can play a role in cancer development is still a new emerging science. Overall, the knowledge seems quite limited in this area.

However, it appears that additional elements have to come into play for the development of turbo cancers:

• Unusual immune cells are present in the cancer environment
• The cancer environment is also rich in glutathione

From the limited available science, the unusual immune cells are M2-like macrophages present with CD163⁺ CD33⁺ PD-L1⁺ biomarkers, abnormal spherical shape and propensity to cluster, and their development can be driven by cancer cells themselves. It appears that these cells interact with IgG4 antibodies as well and this interaction appears necessary for turbo cancer development.

The glutathione is a very important anti-oxidant which under normal circumstances is very welcome for its protective role against harmful chemicals. However, it appears that in a cancer environment that is also rich in IgG4 antibodies, glutathione can help IgG4 antibodies bind to other antibodies and in a process block them from doing their intended purpose. Therefore IgG4 antibodies can bind to genuine anti-cancer antibodies that are meant to help destroy cancer cells, and as a consequence, IgG4 antibodies can inadvertently protect cancers from destruction.

While the precise molecular effects might not yet be clear, it appears that glutathione helps turbo cancer development by helping IgG4s antibodies to adopt a shape that allows IgG4s to bind to other antibodies.

Who develops turbo cancers?

Again, in this area, it appears that science has been limited in being able to pinpoint why only some are at risk of hyperprogressive disease development while others with equally dangerous cancers can instead be effectively treated by the very same IgG4 immune checkpoint inhibitors. The most convincing evidence points to specific genetic predispositions, in other words, specific mutations being found in cancers themselves. One hypothesis proposes that it is these genetic mutations that might aid the cancer environment with glutathione build up that also appears to be needed for turbo cancers.

How serious is this risk?

It is difficult to guess at the moment and I would like to assume that it is small. Why? Because there are conditions that do result in elevated blood concentrations of IgG4 and it is not screamingly obvious that such individuals are getting lots of cancers. One such situation is IgG4-related disease which can result in very high blood levels of IgG4 in comparison to expected normal levels. It is known that people with IgG-related diseases are at elevated risk of cancer development, but this condition is not automatically assumed to result in cancer at all.

Therefore elevated IgG4 blood levels might increase the risk of cancer development, but additional events might be required to precipitate cancer, especially the turbo cancer development.

This suggests that the overall risks with regard to cancer development due to IgG4s being elevated post mRNA vaccination might be small, perhaps even negligible as such risk would require a confluence of numerous biological events to occur.

Nevertheless, the following precautionary steps are proposed.

How should mRNA vaccinated monitor their situation?

There appear to be layers of risks and there could be a hierarchical build up of risk.

The first event that could elevate the risk is attaining blood concentration of IgG4 antibodies which could increase the risk of cancer development. Since it is not established what such concentration could be, at the least, one could focus on blood concentration that is already required as part of diagnosing the IgG4-related disease that appears to have an elevated risk of cancer development. This would suggest a value of 1.3 mg/mL of circulating IgG4 (or 130 mg/dL). Another way that IgG4 antibodies could be reported is as a percentage of total IgG antibody subtypes, and it appears that typically this would be just a few percent at most and can be very small.

I propose that mRNA vaccinated individuals monitor their IgG4 blood concentration to determine if they are going outside of the normal range.

The next layer of risk is having cancer with elevated IgG4 levels followed by cancer with elevated IgG4 levels and glutathione levels. The latter could be a predisposing situation to very dangerous turbo cancers. Please keep in mind that these are suggestions only and should be considered only in conjunction with actual medical expert opinion.

Therefore, mRNA vaccinated individuals with elevated IgG4 levels but without cancer diagnosis could consider:

• Screening themselves for genetic predisposition to cancer (general) and possibly also focus on genetic predisposition towards turbo cancer development such as the genetic mutations that have been proposed in published literature
• Investigate available options for screening for cancer development itself.
• Consider medical intervention options already available to those with IgG4-related disease for reducing their circulating IgG4 levels.
• Avoid supplements that elevate circulating levels of glutathione, including N-acetyl cysteine (NAC), a commonly investigated unofficial option for spike protein detox that also happens to be a glutathione precursor. This should especially be considered if genetic cancer predisposition is uncovered

mRNA vaccinated individuals with elevated IgG4 levels with cancer diagnosis could consider

• Avoid supplements that elevate circulating levels of glutathione and/or consider medical intervention to reduce circulating levels of glutathione
• Screening themselves for genetic predisposition for turbo cancer development
• Consider available medical intervention options for reducing circulating IgG4 levels, especially if genetic predisposition for turbo cancers is uncovered. However, in the context of cancer, this could also be a potentially dangerous option as it suppresses the immune system and would have to be weighed in carefully by the managing medical team

What is the genetic predisposition to turbo cancers?

Unfortunately, this is only an emerging field as hyperprogressive disease is a relatively newly described medical phenomenon. I would imagine it is unlikely that a validated commercial option for such genetic predisposition exists unless some of such mutations have already been previously established to be linked to cancer predisposition (independent of turbo cancers). If such a testing option does not exist, the only remaining option would be to screen specific genes of interest for specific mutations that have already been described in published literature.

Below is a potential starting guide based on the limited literature studied for the development of this article. The hope is to continue expanding on below pooled knowledge over time. Also, please keep in mind that results observed in animals might not be replicable in humans, however, the cell lines used in the animal studies all came from human cancers.

Animal model testing for hyperprogressive disease development:

Published information on molecular mechanisms of turbo cancers (hyperprogressive disease)

Hyperprogressive disease first described after the use of immune checkpoint inhibitors Patient samples show unique immune cell behaviour in cancers CD163+ CD33+ PD-L1+ Abnormal oval shape Aggregation Coinjection of cancer cells and IgG4 induces turbo cancers in mice Fab component of IgG4 cannot induce turbo cancers Turbo cancers in mice provide genetic background predisposition

Potential IgG4 tests (quality not inspected)

These are IgG4 laboratory tests that people have informed me they used to measure their levels. They are only provided here for your convenience and are not recommendations as the quality of offered services has not been studied. Please get in touch with Merogenomics via this website to let us know of a test you used so we can expand this list further.

As this is a precautionary information guide only from a non-medical professional, any feedback is welcome for further improvement of this content due to its potential importance. If you have done a private IgG4 antibody test and you do not see it listed above, you can contact Merogenomics via this website. We appreciate your support.

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