This is the report from the genetics test she had done. She had no symptoms prior of any kind.
Maybe you have heard of people having these symptoms before?

She shared symptoms with me that she had, and said she was hospitalized as she experienced severe ataxia with trouble walking. slurred speech, uncontrollable muscle spasms, extremely dark urine (almost brown—Rhabdomyolysis), heart racing, POTS, nightmare burning pain, inability to stand on her own, severe migraine, sometimes complete paralysis and muscle weakness, dizziness, palpitations. syncope, muscle locking (like I had—myotonia), vision lost (I lost vision in my right eye too), severe tactile hypesthesia—this is what I had too where it felt like I had no finger pads at all, and it was otherworldly pain—she had it too, the list just goes on and on.

She was experiencing what I was in 2021 forward, but hers happened before 2020 with the influenza vaccine.

So what was happening to her was my experience as well. During a widespread channelopathy flare up, the peripheral sensory nerves in the extremities are failing at the exact same time motor nerves are struggling. As the ion channels in the skin receptors temporarily shut down or over fire, you can lose the ability to feel the soft texture of your fingerpads. If you try to move your hands to type during this episode, your brain only receives the deep tissue impact vibration from the bone, making the hands feel completely alien and skeletal while you are actively stumbling or dizzy.

Pure nightmare fuel.

I do not think these things are taught in US based medical schools, and that might be an issue, and worth addressing now because we have how many people going through these nightmare symptoms with no way out?

My friend got lucky because when she was at one of the top hospitals in the US for almost a week, there just happened to be a visiting doctor who was an expert in ion channels. That is what led that doctor who helped her not only live, but address the ion channel disruption.

Some of you might be familiar with Bartter syndrome.
Know anyone who had such an electrolyte crash and maybe they even went into a coma after a vaccine?


Also, mast cells! A lot of people have been saying they have issues with mast cells as a result of infection or injection. Guess what mast cells have? Ion channels. Ion channels are the ultimate on/off switches that dictate when a mast cell activates and dumps inflammatory chemicals. Here is something to read (there is more): Link Between TRPV Channels and Mast Cell Function

Mast cells rely on Potassium and Chloride channels to maintain their baseline electrical charge (membrane potential).

You can have a feedback loop with mast cells and ion channels with the immune system. The mast cell explodes with histamine, which directly binds back onto the surrounding nerves, causing intense itching, local swelling, and severe, burning dysesthesia. Some people have posted on social media they were attempting to go on a mast cells diet, but for people with IBS on FODMAP, the mast cell diet contains so many things that are not allowed on the FODMAP.

These are some things to think about, if you want to go down the rabbit hole and read more about these things, while I go finish writing an opposition brief.

Always always always check with your doctor. This is for educational purposes only. Not meant to DX or RX. Even though it was all my idea, everything I have done, was under a primary doctor’s care. Monitoring had to be done on blood levels, my liver at one time—my doctor was ordering labs to make sure what I was taking other than prednisone, was not impacting me in an adverse event kind of way.

Thanks for your support.

I am in litigation right now for something else rather serious as a Plaintiff, and that is taking up a lot of my time outside of work and other things I am doing.

I just used voice to text, as I am about to go outside for a run on the trails, so its not as well thought out as it should be.

Here is what I posted on Twitter/X:
Ion channelopathy with cGAS STING pathway disruption, mitochondria, macrophages, and mast cells. I didn't write this just for other people. This might be a bit graphic for some. I wrote this for me as well. I healed myself. I have a story that I haven't shared on social media because I thought it best to keep what was going on with me medically separated from the mechanisms I have been posting about for the last 3 to 4 years. I'm waiting to share more because other things happened during this time before I post everything publicly. And it involves other people and it's bad.

https://osf.io/preprints/osf/95u46_v1

I didn't get the help I needed just like other people. I was dismissed by doctors that were supposed to be there to help. When I say dismissed I was released from their care and I was told to shut my mouth by nurses, social workers, and doctors. Messages were sent right to my medical chart where appointments were canceled that were upcoming with neurology at the time, and to leave the area where I was living at the time. Right through my MyChart.

My appointments were canceled and I was released as a patient, after I sought out help for all of these symptoms. By my own providers. They refused to see me and told me to leave te area and go back to the city I lived before. So I did.

I was given zero help where I was living at the time between early 2021 though 2022 until I got to Mayo, and they tried to help before I moved out of the area and started to get some real tests done.

Some people know that I was suffering from severe burning pain what I would call 15 out of 10. I hear about people with diabetic neuropathy. I don't know if it feels like acid has been poured in the inside of their bodies and on the outside. That's what I went through. I don't know if people with diabetic neuropathy experience muscle rigidity to the point where it feels like your legs have turned to stone. That's what I went through. Losing vision in your right eye. Eyes fully bloodshot and feeling like your head's going to explode. Inability to lift anything without struggling, even a glass of water because it feels like doing a daily activity is an Olympic event. Bear crawling up your stairs while you live alone and don't know anyone in the city where you moved to because your legs have lost function. Getting stuck somewhere because your legs won't move. And then all of a sudden they move again. Feeling like you're being pressed up against a stove and then a doctor tells you to take alpha lipoic acid and it makes everything 10 times worse and it feels like you've been poisoned because they don't know mechanisms or cellular biology or even how alpha lipoic acid works they just give it out to anybody whenever they hear the word burning pain. That's incompetence to say the least. And then they say it must be your fault. You're just sensitive.

Feeling like you're being stung by bees all over your body. Feeling like your nerve junctions and the nerves that line your jaw and travel down your arms and surrounding your wrist and your legs feeling like they have been electrified and they are on fire and are pulling in a direction where it feels like you are being strangled on different parts of your body by your own nerves. That was me.

They don't know the actions of alpha lipoic acid they just give it out without thinking.

Having your immune system attack your body. Having inflammation in your esophagus and your stomach to the point you can't eat anymore and every 3 hours you are taking 15 ml of viscous lidocaine because the burning pain is so bad you can't even eat anymore and you look like a skeleton. Just drinking viscous lidocaine right out of the bottle. I was prescribed many bottles of that stuff. Upper endoscopy is done. Lots of biopsies. That was me. I lived off coconut water and cherry juice for 3 months with viscous lidocaine. I drank bottles upon bottles of viscous lidocaine prescribed to me. I heard I am darn lucky I didn't asphyxiate. That's the same stuff they smear on your gums at the dentist before they inject you before you get dental work done. I was just drinking it according to the directions of course.

Not being able to touch anything with your fingers because it feels like you don't have finger pads anymore--not only can you can't play the piano or the ukulele anymore, it feels like the tips of your fingers are missing and the bones of your fingers are touching things. That was me.

SVT. Pots. Pulmonary embolism.
When I had my pulmonary embolism they told me to write my obituary. I was at Mayo because the hospital listed below on that vaccination card where I started to get symptoms 30 minutes after my vaccine dismissed my symptoms and released me as a patient.

Loss of proprioception. Not being able to walk downstairs because you can't sense where you are in physical space anymore. Your body can't detect your movement. That was me.

I was posting all those tweet threads on mechanisms of vaccine harm because it was all I could do and I was using voice to text almost the whole time. That's why there have been grammatical errors because I was using voice to text because I couldn't type without severe pain. That's how I was able to do it so quickly. I was on so much prednisone and then LDN at the same time sleep and I didn't really cross paths more than 4 hours a day for about 2 years.

Barely able to drive your car because you can't physically turn the steering wheel because your arms won't respond and it feels like you're no longer part of your body or have control over it. That was me.

That was me back in around 2021 and 2022, and it continued into 2023. Prednisone was the only thing in high doses that made the pain back off and disrupted the symptoms and 5 mg a day was not anything. Higher doses did.

The doctor that prescribed it and I talked about the reality of being on such high doses of Prednisone for so long and with the consequences could be and I said it was far better than suffering those symptoms I was having and to kick that can down the road.

Being offered no help except LDN or ivermectin by some.

So then you start using yourself as a guinea pig.

And you get to a doctor that wants to help so they do punch biopsies and they can't get you numb because of course you have this issue with your ion channels, but they don't know it at the time, so they're doing punch biopsies, and they can't get you numb, and you have excessive bleeding and they can't figure out why. So you're biting a rag in your mouth while they do punch biopsies digging down into your leg because they can't get you numb.

Went for a lumbar puncture and it's not by an actual doctor it's by some nurse or PA and she hits the nerve in your back and oh it's an accident can't believe that happened. And then you can't walk well because she hit the nerve in your back that controls your right side of your body. So for a week you're stumbling around. That was me.

And the tests for the small fiber neuropathy punch tests come back showing barely out. And the lumbar puncture results come back fine and they aren't seeing any protein bands.

So then they say it's just functional neurological disorder and more than one doctor tells you a switch in your brain is bad.

Wow that's medicine and it's finest isn't it? So I got told I had functional neurological disorder and they couldn't do anything for me. Bullshit.

Nerve conduction tests are a nightmare and it only shows that something's out in your right ankle and that would make sense because back around mid-2000s I was playing disc golf and I did a side running through and I overstepped the pad, rolled my ankle a full 180, bounced, and landed back on it and it fully shredded the outer ligament. Thank goodness I had one of the top surgeons in the state at a private clinic do the surgery and I was running again my first 5k about 5 months later. I had an amazing orthopedic surgeon. Dr McCormick. That's me.

And your symptoms are not that of multiple sclerosis and they aren't that of a diabetic neuropathy and they are so severe it's impacting your whole body and no one you talk to no matter where they are knows what the hell an ion channel dysfunction even is.
That was me.

You get Lyme's test done twice with all these extra panels attached to it. Mono. Everything you can think of. That was me.

So you start researching because you're in the worst pain of your life and no one's coming for you. No one's helping except saying to take ivermectin LDN and get a nicotine patch going on your arm and just suffer.

That was me.

At one point, I was on 40 to 60 mg of prednisone a day. High doses of prednisone for me was the only thing that helped me and decrease the symptoms down to the point where they were just in the background and I was able to carry on with life.

Then I got to the point where it was just 20 mg a day. Sometimes it would flare even harder so I was back on 30 to 40 mg a day of prednisone. When I mean flair that's feeling like almost your entire body inside and out is being doused with acid that you would use in your chemistry lab. Had a dexa scan because there was fear that bone demineralization was going to happen because of the high prednisone dose. Thank goodness the dexa scan came back all green.

Refused IVIG. No one would give me IVIG, they kept saying there was a risk of clot did it matter if I saw an MD neurologist it didn't matter.
So then I would get some people messaging me saying I should travel to Florida. For what more ivermectin?

Then I started to use capsaicin in a high percentage dose on the outside of my body where I was feeling this burning pain because I was reading not just about the c nerve fibers involved, but that it also acted on ION channels.

I begged for genetic testing for polymorphism of ION channel or mutation whether it be acquired de novo or not and I was denied the genetics testing and just told to put a nicotine patch on my arm.

I continued to use high dose capsaicin spray which meant having to wear a mask and apply it outside because it seems to work better than the cream.

That was taking the edge off. I also learned that when they say in the instructions not to take a shower for an hour after applying that it is not true and you should wait a lot longer than that!

And I begged for a drug that regulates ion channels that is not something typically given to people. Not a calcium channel blocker. Something very different. And my doctor gave it to me. I was started on the lowest dose possible because there was a chance we had concern over arrhythmias or something happening.

And I started researching other things, and I always ate well typically whole food most of my life and I've never been one to drink because I can't I don't feel well if I do. I used to be at martial artist and a distance runner. I also do have EDS that was confirmed before covid hit. Hashimoto's is what I also had for years which I take levothyroxine and Liothyronine.

I had all these people telling me to take zinc or go on some protocol or do a fecal transplant blah blah blah blah blah blah blah blah blah blah blah blah blah blah blah and it was all BULLSHIT.

And I went from being able to run 8 to 10 miles a day to not being able to turn the steering wheel in my car or touch anything without feeling severe burning pain.

I tried all the protocol that was out there that the so-called doctors have and it did nothing for me.

LDN was actually a nightmare for me. Even at the 0.1 mg micro dose I was suffering insomnia as a side effect and also it did something that it shouldn't have even when we tried to slowly increase it and I wonder if it was because I was taking it at the same time as prednisone and it was hitting my opioid receptor and let's just put it that way.

So when people were asking how in the world was I making all of these posts all the time about science it is because I was taking very high doses of prednisone. I was using voice to text almost the whole time. And for someone who can't even take Claritin non-drowsy without going to sleep for 6 hours one can imagine what it must be like for someone to take roughly 20 to 40 mg of prednisone a day over span of a couple of years at least.

I started the DNA methylation diet but with some changes to it to stabilize ION channel and force my body to undergo mitophagy. A lot of people talk about autophagy. I developed a protocol to stabilize ION channel, force mitophagy, and stabilize cGAS STING pathway. It's a combined specialized synergistic diet utilizing chemicals found in certain foods and creating synergy for higher bio availability. I also targeted heme oxygenase 1.

Another thing that happened was around 2024 I came up with a drug design for a drug to permanently remove Spike protein expression at the reservoir source.

Some doctors and scientists and a professor were already defaming me and committing tortious interference-- I think people know who those people are based on their tweet threads calling for my murder saying that I was a plant or some psyop. These are people who define themselves as being part of the medical freedom movement. They also called to have me fired from a research project I was working on. And they got me fired. The same people that say they are good people here on the internet are doing all of these things. They knew full well of what was going on with me medically and yet they came at me, but that's probably because I have evidence of massive fraud.

So in 2024 I designed a drug because that's what I used to do for a living. I met with a patent attorney in California who is very good. I met with a CDMO four times in 2025 and they agreed to make the drug and I got statement of work. I met with funders I met with animal testing group and if it continued to move forward beyond prototype stage I met with clinical trial company twice. That was over a year ago. They agreed to make it over a year ago.

And now it is August 5th 2026 and I've been crying so much. It has been 2 months since I have stopped the prednisone and the other drug I was on. I have not had any severe burning pain, any pots, SVT, muscle weakness, rigidity--none of it.

It's gone. And every day I wake up thinking that it's going to come back. I'm going to wake up and it's all going to come back and the nightmare is going to start over but it hasn't.

I have an appointment coming up with my doctor to repeat labs to see what we see.

I've just used voice to text to type all of this here on Twitter where it probably doesn't belong and it should be in a sub stack or a preprint on exactly what has happened, all the tests that were done, the exact protocol I developed for myself, the drug I designed, the other medication I took, gathering all the labs together and looking at how things have changed, etc.

None of this is medical advice. I am not a medical doctor but I do have five majors and I used to work on an operations team with scientists designing the milestones and the workflows for a living custom designing drugs for genetic disease and cancer.

I also designed a diet that is highly targeted at stabilizing ion channels and doing the things that I said I did. I designed the protocol. I designed the diet. I designed the drug.

And right now all my symptoms are gone. I'm 2 months out from taking any prednisone or any other drug I took.

Will probably write a more thought out substack and place it in a preprint with a DOI on it shortly but I'm super busy right now.

Everyone is different and people that suffer from Spike protein issues or other issues are different from one another. People have different genetics going on. People have different responses to different things.

This is not meant to diagnose anyone or treat anyone.

But I know people are suffering and I was threatened by people in the medical freedom movement right to my phone so you can just continue taking your ivermectin or doing whatever you're doing.

I'm going outside for an 8 mile run.

Apparently a bunch of people are going to Japan and they're all healed now saying except no substitute.
Congratulations to you. Glad you found something that works.

I did too. But it's not your protocol. 100% symptoms gone.

I'm at 100% today. Zero symptoms. All gone. Over 2 years of a nightmarish hell. 2 months free of all drugs except for my thyroid medication that I need to have.

Have a good day.

I need to expand on this in regards to cGAS STING implications of DNA plasmid activation without integration, creating hypermethylation, leading to myocarditis, autoimmune disease, and cancer.

I will expand more here (later). I was going to place this in the paper I have been working on, but it deserves a paper all on its own.

HYPOTHESIS/PROPOSAL: MODIFICATION of EXISTING STUDY: EPIGENETIC CLOCKS as TRACKING MECHANISMS FOR INJURY and DISEASE--WITH or W/OUT INTEGRATION for FINDING CELLULAR and EPIGENETIC AGE and DAMAGE by RNA/DNA/LNP--TRACK INJURIES "BY TIME"?

(Length of Iliad post)

*In cancers, loss of expression of genes occurs about 10 times more frequently by hypermethylation of promoter CpG islands than by mutations.*

This is heavy science. Use your favorite AI model to copy and paste this for a "explain it to me like I am 12" version. Use your Grok, etc.

A longitudinal study was done and submitted in June of 2022 on those with severe covid and those who received vaccination. During this time, COVID was more virulent--produced more disease compared to other strains. Additionally, those used in this study who received vaccination do not appear to have suffered any type of side effect from vaccination that was immediately apparent.

"Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination"

https://pmc.ncbi.nlm.nih.gov/articles/PMC9203887/

Pang, A. P. S., Higgins-Chen, A. T., Comite, F., Raica, I., Arboleda, C., Went, H., Mendez, T., Schotsaert, M., Dwaraka, V., Smith, R., Levine, M. E., Ndhlovu, L. C., & Corley, M. J. (2022). Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination. Frontiers in genetics, 13, 819749.

First, a bit about what epigenetic clocks are and how they are useful in studying diseases, like cancer. Second, we are going to look at some highlights form this study (link below) and then we are going to look at  other epigenetic "clocks", CpG islands, and some other factors (more are involved with cGAS STING, APOBEC and other factors that are not discussed here)--not just with aging, but autoimmune disease, CANCER, how one might combine this study design with some other factors, and do some different tests to elucidate determinants of disease states.

Epigenetic Clocks and Their Role in Biological Aging

Epigenetic clocks are biomarkers of biological age that rely on  DNA methylation patterns to predict an individual’s physiological age based on their epigenetic modifications.

The most well-known epigenetic clocks include the Horvath clock and the Hannum clock, which focus on specific sets of CpG (cytosine-phosphate-guanine) sites across the genome.

These clocks show massive associations with age-related phenotypes, chronic diseases, and mortality risk, reflecting the cumulative impact of various environmental factors, lifestyle choices, and biological stressors on the aging process.

CpG islands (CGI) which appear in segments of our genome that are rich in the C's and G's in our DNA--are regions with high frequency of cytosine and guanine nucleotides, and  higher frequency of CpG dinucleotides than the rest of our human genome. CGIs are found in or near the promoter regions of genes. The promoter is where transcription begins.

These can be methylated--hypermethylated. This can happen without integration, and it can happen with what is called TRANSIENT EXPRESSION.

Aberrant methylation of cytosine nucleotides within CGIs can lead to cancer formation.

In cancers, loss of expression of genes occurs about 10 times more frequently by hypermethylation of promoter CpG islands than by mutations.

Mechanisms of Epigenetic Aging: DNA Methylation

DNA methylation is the addition of a methyl group to the cytosine bases of DNA, mostly occurring in CpG dinucleotides--which can regulate gene expression by influencing the accessibility of transcription factors to DNA.

Hypermethylation is an increase in methylation levels at specific genomic regions, like promoter regions of genes. CpG islands have a unique placement when it comes to our promoters in our Genes.

Hypermethylation of promoter regions generally leads to gene silencing, while hypomethylation can activate gene expression. As individuals age, changes in the methylation patterns across the genome, and this can be tracked, and allow for studying aging, but that is not all.

When a promoter region becomes hypermethylated, the gene it regulates can become downregulated or silenced, disrupting normal cellular pathways causing diseases, including cancers, autoimmune disorders, and chronic inflammatory conditions. An example would be hypermethylation of tumor suppressor gene, which could drive oncogenesis (CANCER) by preventing the expression of proteins that would usually inhibit uncontrolled cell growth.

In the first wave which produced more virulence, hypermethylation of genes associated with the immune response may have led to impaired immune function, potentially exacerbating the effects of Sars COv 2 in some people, which manifested as an altered inflammatory response, contributing to the severity of the disease.

But what about the vaccines? We'll get there.

The study--how covid might have impacted epigenetic clocks. The researchers looked at SARS-CoV-2 infection and mRNA COVID-19 vaccinations influence epigenetic clocks—specifically, PCPhenoAge, PCGrimAge, and other measures of biological age—among individuals of varying ages.

(they did not get the right groups of people for the vaccinations--they also MISSED some huge factors)

This study involved examinations of 21 participants aged 18 to 73, with blood-based DNA methylation data collected within a six-month timeframe.

The study showed that specific epigenetic changes, particularly hypermethylation of the CARD14 gene, were associated with alterations in immune cell composition, notably in CD8 T cells. This hypermethylation shows a larger dysregulation of immune function post-infection. Additionally, they  identified 756 differentially methylated CpGs related to COVID-19 exposure, with many loci enriched in transcriptional gene sets derived from existing SARS-CoV-2. ACIN1, a gene involved in chromatin condensation during apoptosis, showed a decrease in methylation post-COVID-19.

Methylation changes were linked to 516 protein-coding genes involved in pathways like cellular glucose homeostasis and thyroid hormone signaling.

The study authors were probably also not aware, that the vaccines produced by Pfizer and Moderna contain DNA plasmid contamination.

*******************************************************************

Now, what if we take parts of this study, and then fuse with some other tests? What could we find out?

(this is a social media post--if you are in a lab, maybe you could edit/correct/make some changes on some things.  Here we go.)

Temporal Investigation of Vaccine injuries

Epigenetic clocks and molecular scars can help estimate the timing and impact of injury like myocarditis, activation of autoimmune disease, tumor clonal expansion, and other injuries via prolonged genetic/epigenetic dysregulation post-vaccine, particularly if  DNA/RNA persists or integrates.

Beyond recognition of epigenetic changes, there may be a way to go back in time, and look and see, when things occurred, molecularly. You could take blood or tissue, without knowing if it came from someone injured, run some tests, and see if there was a hypermethylation, and see if gene expression occurred and what type that would happen in a CpG island adjacent to a promoter region that encodes for--an immune system protein.

In the basic terms, one wonders, if you could focus on Epigenetic and Transcriptomic Analysis.

One could look at  DNA methylation analysis by performing bisulfite sequencing on tissues like blood (for systemic immune response markers), heart tissue (for myocarditis markers), and potentially tumor biopsies (if clonal expansion is suspected)--focusing on regions associated with immune response genes, oncogenes, and tumor suppressor genes to track the changes.

Next one would look at targeted methylation panels  that focus on known immune-modulated genes and cancer-related genes to determine epigenetic shifts linked myocarditis, autoimmune, or tumorigenesis.

Then one could look at RNA-seq and single-cell RNA-seq and perform gene expression profiling of blood cells, heart tissue, or tumor samples looking at the long-term effects of vaccine-induced inflammation or tumor growth When using single-cell RNA-seq, this can elucidate fine tuned details about cell-specific responses, especially in immune cells (T cells, macrophages) or in expanding tumor clones.

To look at cancer, one could look at clonal tracking and somatic mutations through whole-genome or targeted sequencing:
Detect clonal mutations in key cancer-related genes (KRAS, MYC, or TP53) in tumor tissues or blood (for circulating tumor DNA). Mutations or integration of vaccine-related DNA could indicate clonal expansion triggered post-vaccine. However, this is a very basic approach (the WGS). Single-cell sequencing could track tumor heterogeneity and how it evolved over time. This is all known and basic level.

However, if one looks at methylation states in specific CpG islands, this may assist.

Tracking CpG Methylation in Myocarditis

This involves  immune-mediated damage to heart tissue, with immune-related genes (IL-6, TNF-a, TLR pathways) likely undergoing epigenetic modifications.

Even one year after vaccine administration, you could find hypo- or hypermethylation at CpG islands near the promoters of inflammatory cytokine genes in immune cells (like T cells, macrophages) or heart tissue. Hypomethylation (less methylation) in these islands might indicate prolonged gene activation, showing the lingering effects of myocarditis.

Hypermethylation (more methylation) could suggest suppression of regulatory pathways that might normally limit inflammation.

Analyze CpG Methylation in Immune Genes

For myocarditis, look for methylation changes in CpG islands of:

Cytokine genes

 IL-6, TNF-a, and IFN-y.

Toll-like receptor genes

TLR3, TLR7, TLR9.

Immune regulatory genes

 Genes related to regulatory T cells (Tregs) or macrophage polarization (M1/M2).

***Genes involved in the innate response, like  cytokines (TNF-α, IL-6, IL-1β), Toll-like receptors (TLRs), and interferon-related genes, show hypomethylation early in response to infection/injection.

 This allows for rapid transcription and the production of pro-inflammatory molecules.

Methylation patterns of innate immune genes change within hours to days of activation, making it possible to detect these events shortly after the immune system is engaged.

****Epigenetic Clocks for Innate Immunity--These clocks might be used to  track the rate of cytokine gene methylation changes to estimate how recently the immune system was triggered by the RNA or DNA vaccine.

EXAMPLE: A loss of methylation at the TNF-a promoter suggests rapid immune activation that may have occurred recently.

Over time, there are epigenetic changes in genes controlling T-cell differentiation, antigen presentation, and memory T-cell formation.

Hypomethylation of T-cell genes
In T cells, specific genes associated with T-cell receptor signaling and cytokine production become hypomethylated during the adaptive response.

These changes may last weeks to months after the initial immune challenge, making them suitable for longer-term immune clocks.

Regulatory T cells (Tregs), which express FOXP3, are important for shutting down immune responses and preventing autoimmunity. If FOXP3 is involved, autoimmunity might now be engaged compared to initial response.

This means, you might not even need to know the exact date someone had vaccination to know when injury occurred.

FOXP3 and Regulatory T Cells (Tregs)

FOXP3 is a key transcription factor that controls the development and function of regulatory T cells (Tregs). Tregs  maintain immune tolerance and prevent autoimmune disease by suppressing excessive immune responses.

FOXP3 Methylation and Autoimmunity

Methylation status of the FOXP3 gene is an important indicator of Treg activity.

In active Tregs, the FOXP3 promoter is typically hypomethylated, allowing for high levels of FOXP3 expression, which promotes the suppressive function of these cells.

Hyperactivation of the immune system!

 If the immune system is highly activated--after infection or injection, Tregs are recruited to help resolve the inflammation.

 FOXP3 hypomethylation is a good indicator of active immune regulation.

Hypomethylation of FOXP3 means Tregs are actively trying to control an immune response.

This could indicate a chronic inflammatory state or an attempt to prevent autoimmune reactions.

FOXP3 Hypomethylation and Autoimmune Disease

In cases where Tregs are insufficient or dysfunctional, autoimmunity can develop. If one observed FOXP3 hypomethylation, it might indicate that Tregs are being activated but are unable to fully control the immune response.

In some cases of autoimmune disease, Treg function may be impaired, leading to insufficient suppression of autoreactive immune cells.

This can be seen in conditions like autoimmune myocarditis or other autoimmune diseases like AIDP, Hashimotos, and other immune diseases.

FOXP3 hypermethylation could be a marker of reduced Treg activity, meaning that the immune system may be out of control, contributing to autoimmune disease or chronic inflammation.

Thus, FOXP3 methylation status could be used, in tandem, with time tracking.

 In the early stages of an immune response, important cytokine genes (e.g., IL-6, IL-1β, TNF-α) often become hypomethylated, leading to increased expression and the release of inflammatory mediators.

These  genes involved in T-cell activation and B-cell function also become hypomethylated. This allows for the differentiation of helper T cells, cytotoxic T cells, and the development of memory T cells.

CpG Islands in Immune Genes

Many immune genes contain CpG islands near their promoters. In a resting state, these regions may be methylated, keeping the genes turned off. However, during an immune response, these islands can become demethylated, activating the gene.

Tracking Hypomethylation Over Time

The timing of these changes can help track the progression of an immune response or the development of autoimmunity.

Acute response

Early hypomethylation in cytokine genes means a  recent immune event.

If hypomethylation persists in certain immune regulatory genes (IL-10, FOXP3), that probably indicates an ongoing immune dysregulation or autoimmunity.

How to Measure Epigenetic Timing in Immune Responses

Epigenetic clocks for immune cells

These clocks track methylation changes over time in genes related to T-cell activation, B-cell function, and cytokine production.

By assessing the methylation patterns at various time points, researchers can estimate how long ago an immune response began.

Once again, one could lean towards sequencing.

Single-cell sequencing

Using single-cell RNA-seq or ATAC-seq combined with bisulfite sequencing might measure gene expression and methylation status at the single-cell level.

This would identify which immune cells are activated at specific times post-vaccination.

This means one might be able to track, even without knowing the time of vaccination data point exactly, when things started, to a degree.

THE HORVATH CLOCK (and others):

Horvath Clock

The Horvath clock is a type of epigenetic clock developed by Dr. Steve Horvath in 2013. It measures biological age based on the methylation patterns of specific CpG sites in the DNA, and it can predict the biological age of many tissues and organs in the body.

DNA methylation is a key part of the clock. Methyl groups attach to CpG sites (regions where a cytosine nucleotide is followed by a guanine nucleotide) and regulate gene expression. As people age, their DNA methylation patterns change in a highly predictable way at certain sites, which allows the Horvath clock to estimate the biological age of cells and tissues, often more accurately than chronological age.

The Horvath clock is based on methylation at 353 CpG sites spread across the genome. By analyzing these sites, the clock gives an estimate of biological age, which may differ from a person's chronological age.

The difference between biological and chronological age is referred to as epigenetic age acceleration. A higher biological age might suggest increased susceptibility to age-related diseases or conditions like cardiovascular disease or cancer.

A scientist might be able to tie together the Horvath clock, CpG islands, methylation states of key areas near promoters that were responsible for gene expression related to cancer, autoimmunity, and other disease states.

 Immune System Clocks

The immune system clock is a concept based on the idea that the immune system’s age can be tracked through its own specific methylation patterns and cellular signatures. It focuses on immune cells and how their DNA methylation changes over time due to aging or responses to environment, like infections, or vaccines. Immune age doesn’t necessarily match chronological age. For instance, someone with a chronically activated immune system (e.g., due to infection or autoimmune disease) may have an immune system that appears "older" than their chronological age.

Epigenetic changes in immune cells, such as T-cells and B-cells, can reveal how long ago an immune response occurred and how it has evolved.

Over time, as people age or experience repeated immune system activations, the epigenetic landscape of T-cells changes, reflecting their "age" and functional state. Specific T-cell subtypes (like naive, effector, or memory T-cells) show distinct methylation profiles based on their experiences.

These are a bunch of clocks for tracking when methylation occurred:

 Horvath’s Clock

epigenetic clock based on DNA methylation patterns across various tissues--can  predict biological age.

Hannum's Clock

Another DNA methylation-based clock developed by Hannum et al., which focuses on blood cells. It uses a different set of CpG sites compared to Horvath’s clock--useful for estimating biological age and assessing changes in blood-related conditions and immune function.

PhenoAge Clock

Developed by Levine et al., this clock predicts biological age based on DNA methylation and is designed to be more closely related to phenotypic health-focuses on age-related health metrics, including inflammation and immune status, making it relevant for studies on immune system changes and aging.

GrimAge Clock

A DNA methylation clock developed by Lu et al. that predicts lifespan and healthspan based on epigenetic markers linked to mortality and age-related diseases--like biological age associated with cancer risk and immune dysfunction.

T-cell Senescence Clock

 specifically designed to measure the epigenetic changes associated with T-cell senescence, a hallmark of immune aging--looks at  T-cell function in relation to  autoimmune diseases or cancer.

Cancer-Specific Methylation Clocks

These are biomarkers for cancer diagnosis and prognosis, to track epigenetic changes in tumors over time

EpiClock

 integrates multiple epigenetic features to assess cellular age and function, with an emphasis on immune cells.

Here are some key genes that have CpG islands right in front of them, that can be influenced

TP53: leading to loss of tumor suppression.

CDKN2A (p16INK4a):  hypermethylated in melanoma, lung cancer, and pancreatic cancer, resulting in cell cycle dysregulation.

BRCA1: Hypermethylation in breast and ovarian cancers, affecting DNA repair pathways.

VHL (Von Hippel-Lindau): Methylation--renal cell carcinoma by inactivating this tumor suppressor gene.

MGMT: Hypermethylation glioblastoma

PTEN:  prostate cancer.

MLH1:  Lynch syndrome-related cancers

MBD4: many cancers

SFRP1:  colorectal cancer, affecting the Wnt signaling pathway.

RASSF1A:  lung cancer and other malignancies, impacting cell cycle regulation and apoptosis.

DAPK (Death-Associated Protein Kinase): Hypermethylation can lead to loss of apoptotic regulation in several cancers.

ER (Estrogen Receptor): breast cancer can result in altered hormone signaling.

PR (Progesterone Receptor): Similar to ER,  in breast cancer.

CTLA-4: lupus and rheumatoid arthritis.

FOXP3:  autoimmune disorders.

BDNF (Brain-Derived Neurotrophic Factor):  various neurological conditions, including depression and schizophrenia.

APC (Adenomatous Polyposis Coli): Hypermethylation linked to colorectal cancer, involved in Wnt signaling.

STK11 (LKB1): Hypermethylation is associated with Peutz-Jeghers syndrome and lung cancer.

TGFBR2 (Transforming Growth Factor Beta Receptor 2): Hypermethylation is common in colorectal cancer and is associated with TGF-β signaling disruption.

NDRG1: Involved in cancer metastasis, hypermethylation can lead to decreased expression in various cancers.

SOCS1 (Suppressor of Cytokine Signaling 1): Hypermethylation linked to several hematological malignancies, affecting immune response.

DAPK1: Associated with the apoptotic process, hypermethylation is observed in various cancers.

Genes Involved in DNA Repair and Genomic Stability

XPF: Hypermethylation can affect DNA repair processes in cancers.

FANCF: Associated with Fanconi anemia, hypermethylation may lead to increased cancer susceptibility.

BRCA2: Involved in DNA repair; hypermethylation may affect breast and ovarian cancer susceptibility.

Genes in Development and Differentiation

HIC1 (Hypermethylated in Cancer 1): Hypermethylation in various cancers; involved in transcriptional repression.

GATA5: Hypermethylation linked to colorectal cancer, influencing differentiation processes.

SALL3: A transcription factor that can be hypermethylated in Wilms tumor and other cancers.

Additional Cancer-Related Genes

PAX5: Hypermethylation is associated with B-cell malignancies.

RARB (Retinoic Acid Receptor Beta): Linked to breast cancer

FHIT (Fragile Histidine Triad): lung cancer and other malignancies.

NDRG2: expression in tumors.

PRDM1 (Blimp-1):  lymphomas and  immune responses.

AR (Androgen Receptor):  prostate cancer

CDH1 (E-cadherin): epithelial-to-mesenchymal transition in cancers.

IL-2RA (CD25):  autoimmune diseases like multiple sclerosis.

Neurological and Psychiatric Disorder Genes

NRG1 (Neuregulin 1):  schizophrenia.

SLC6A4 (Serotonin Transporter): depression susceptibility.

MECP2:  neurodevelopmental disorders.

MMP2 (Matrix Metalloproteinase 2):  cancers affecting tissue remodeling.

TET2: blood cancers like AML (Acute Myeloid Leukemia).

But how could this occur without integration?

transient exposure to linearized DNA within lipid nanoparticles, can cause transient expression AND cause HYPERMETHYLATION of the CpG islands associated with specific promoter regions in our genes!

Once again, CpG islands are regions rich in CG dinucleotides, typically located near gene promoters, and their methylation status often regulates gene expression

cGAS STING!

Linearized plasmid DNA can induce CpG island hypermethylation through cellular stress and immune responses triggered by foreign DNA recognition. When introduced into cells, linearized DNA activates DNA-sensing pathways, like cGAS-STING pathway, which can initiate downstream epigenetic changes, including methylation of CpG islands at gene promoters. In response to perceived DNA damage or foreign DNA presence, DNA methyltransferases (DNMTs) may be recruited to CpG-rich promoter regions, catalyzing hypermethylation, leading to chromatin condensation, preventing the binding of transcription factors and silencing gene expression. Additionally, immune responses induced by exogenous DNA may activate inflammatory signaling, which can epigenetically modify host genome regions, particularly CpG islands in promoters of genes involved in immune regulation or DNA repair (CANCER)

Ultimately, hypermethylation of CpG islands alters promoter activity by repressing transcriptional initiation, effectively silencing or downregulating genes involved in stress responses, immunity, or cell cycle regulation.

When cGAS-STING is activated by plasmid DNA, it triggers an immune response, leading to the recruitment of DNA methyltransferases (DNMTs) to CpG islands at gene promoters. This causes hypermethylation, which silences gene expression by blocking transcription factor binding and promoting chromatin condensation

( This  proposal needs correction by those who may perform in a lab and probable edits. )

So now we look at another study:

Plasmid DNA is a contaminant in 💉🦠🧬and is double stranded (ds) DNA: it contains CpG oligonucleotide (ODN).

A STUDY: Researchers found differences in cellular responses+ different gene responses to ds DNA and its effect on GENE MODIFICATION--transient transfection.

The STUDY "Differential cellular responses to exogenous DNA in mammalian cells and its effect on oligonucleotide directed gene modification" Igoucheva, O et al. Gene therapy vol. 13,3 (2006): 266-75. doi:10.1038/sj.gt.3302643 https://sci-hub.se/10.1038/sj.gt.3302643

(this is from a twitter thread I did).

Researchers wanted to know how cells respond to the presence of double-stranded DNA (dsDNA), and the influence that different dsDNA (different sizes/types) have on different cellular processes, and the impact on different genes. They found a variety of results.

They used two types of cell lines, NIH3T3 and CHO-K1, and introduced plasmid dsDNA into the cells. The introduction of dsDNA was achieved by transient transfection, where external genetic material (in this case, dsDNA) is introduced into cells (DNA/lipid complex).

After adding the dsDNA to the cells, the researchers observed how the cells' gene expression changed, especially the transcriptional response, which means they studied how genes were "turned on" or "turned off" in response to the presence of dsDNA inside the cells.

The researchers analyzed the activity of various genes in response to dsDNA. The genes they examined are associated with processes like DNA repair, cell cycle regulation, apoptosis (cell death), and other cellular responses, such as uncontrolled cell growth, and cancer.

They found "cell-type dependency". Different cell types exhibit remarkably different rates of gene modification in response to the dsDNA.

Introduction of dsDNA activated transcription of many genes involved in DNA damage signaling and repair.

Long dsDNA induced genes responsible for sensing DNA damage, like ATR-dependent signaling, nucleotide excision repair (NER), and mismatch repair (MMR).

ATR (ataxia telangiectasia and Rad3-related) was identified as the primary sensor of DNA replication blockage resulting from lesions by DNA adducts, UV, and DNA synthesis inhibitors.

The study observed a strong induction of ATR and several genes participating in ATR-dependent signaling.

ATR is paramount in maintaining stability of the genome.

Mutations or dysregulation of ATR can lead to disease and cancer.

ATR is also part of the activation of cell cycle checkpoints. Dysregulation is another hallmark in cancer. ATR is also a tumor suppressor. Loss of function or mutations in ATR may contribute to the development of cancer.

This table shows transcription in response to the presence of dsDNA in the two cell types. The data is for various genes associated w/ different cellular pathways. The fold induction values represent ratio of intensity of each gene in cells transfected.

The ones that are related to cancer: ATR (Ataxia Telangiectasia and Rad3 Related): Implication in Cancer: Dysregulation of ATR has been associated with genomic instability and cancer. ATR mutations or altered expression can contribute to uncontrolled cell proliferation.

ATM (Ataxia Telangiectasia Mutated): ATM is involved in DNA repair and cell cycle control. Mutations in ATM are linked to an increased risk of cancer. ATM is a tumor suppressor, and its dysfunction can lead to genomic instability and cancer development.

Cyclin-Dependent Kinase Inhibitor 1A (p21): p21 is a cyclin-dependent kinase inhibitor, regulating the cell cycle. p21 acts as a tumor suppressor by inhibiting cell cycle progression. Dysregulation can lead to uncontrolled cell division and contribute to cancer.

Bcl-2 Homologous Antagonist/Killer (Bak): apoptosis and regulation of cell death. Dysregulation of apoptosis is a common feature in cancer. Altered Bak function may affect the balance between cell survival and death, contributing to cancer development.

B-cell Leukemia/Lymphoma 6 (Bcl6): cell cycle regulation and apoptosis. Aberrant expression of Bcl6 is associated with lymphomas and other cancers. It can promote cell survival and inhibit apoptosis, contributing to tumor development.

Growth Arrest and DNA-Damage-Inducible 45 (GADD45): cell cycle arrest and DNA damage response. GADD45 genes play a role in preventing genomic instability. Dysregulation can contribute to cancer by affecting cell cycle control and DNA repair.

p53 (Tumor Protein 53): tumor suppressor, regulating the cell cycle, DNA repair, and apoptosis. Mutations in p53 are common in various cancers. Loss of p53 function allows for uncontrolled cell division and survival of damaged cells, contributing to cancer progression.

BRCA1 and BRCA2: DNA repair.

Mutations in BRCA1 and BRCA2 are associated with an increased risk of breast and ovarian cancers. genomic integrity. *** Tumor Necrosis Factor (TNF): apoptosis and inflammation. Dysregulation of TNF signaling : chronic inflammation and cancer.

Telomerase Reverse Transcriptase (TERT): maintains telomere length. Activation of telomerase, including TERT, is common in cancer cells, allowing for unlimited cell division. unlimited cell division

Xeroderma Pigmentosum Genes (XPA, XPC): DNA repair. I Mutations in XPA and XPC are associated with an increased susceptibility to skin cancer. These genes play a crucial role in repairing DNA damage caused by UV radiation.

Nuclear Protein and Cellular Processes— nuclear protein (PA26) associated with the gene suggests involvement in nuclear activities (nucleus). (BF537978) may be under the regulation of the P53 protein. Both were impacted in this study by the dsDNA, including other genes.

other studies exist on the impact of dsDNA on signaling pathways, and specific genes.

cGAS STING and APOBEC:

cGAS STING is part of this, and so are APOBEC enzymes (and macrophages)

For a refresher and a very long read on cGAS STING activation without any kind of integration happening, read this long novel:

What we are look9ing at, is combining the cGAS STING activation pathway, which can occur with DNA plasmids (longer ones even in smaller amounts will drive the highest activation intensity (and spike, double stranded RNA, double stranded DNA, bacteria, and some charged elements too), that gets activated, then this pathway is involved with APOBEC enzymes.

DNA Plasmid Detection by cGAS

• Cytosolic DNA from foreign sources (like DNA plasmids, viral DNA, or self-DNA from damaged mitochondria or nuclei) is usually considered abnormal by the immune system.

• cGAS (cyclic GMP-AMP synthase) is a cytosolic DNA sensor that detects these foreign or mislocated DNA fragments.

• When DNA plasmids enter the cytoplasm, cGAS recognizes double-stranded DNA (dsDNA) of a particular length (usually >40 base pairs) and becomes activated.

• Upon activation, cGAS synthesizes a second messenger called cyclic GMP-AMP (cGAMP) from ATP and GTP. This cGAMP molecule is a key activator of the STING protein.

STING Activation and Immune Signaling

• STING (Stimulator of Interferon Genes) resides on the endoplasmic reticulum (ER) and gets activated by the cGAMP produced by cGAS.

• Once STING is activated, it translocates from the ER to the Golgi apparatus, where it serves as a platform to recruit and activate other key signaling molecules like:

  • TBK1 (TANK-binding kinase 1)

  • IRF3 (Interferon Regulatory Factor 3)

• STING also activates NF-KB, a transcription factor that promotes the expression of proinflammatory cytokines like TNF-a, IL-6, and type I interferons

• This inflammatory response can be beneficial in clearing infections, but when chronically activated (as with persistent DNA plasmid exposure), it can lead to tissue damage, immune dysregulation, and promote disease.

APOBEC Activation and DNA Editing

• APOBEC (Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like) family of cytidine deaminases is part of the immune system's response to foreign DNA.

• APOBEC enzymes are usually upregulated in response to viral infections and inflammatory signals (such as those triggered by the cGAS-STING pathway).

• These enzymes deaminate cytosines in single-stranded DNA (ssDNA), converting cytosine (C) to uracil (U). This can lead to C→T or C→G mutations during DNA replication.

  • APOBEC3A and APOBEC3B, in particular, have been implicated in cancer due to their mutagenic potential.

  • They preferentially target single-stranded DNA, which is often transiently exposed during DNA replication, transcription, or repair.

  • Mutations caused by APOBEC enzymes often leave a characteristic mutational signature, known as the APOBEC signature, in the genome, contributing to genomic instability.

Chronic Inflammation, ROS, and Epigenetic Changes

• Persistent activation of STING induces a chronic inflammatory environment with high levels of cytokines and reactive oxygen species (ROS).

• ROS causes oxidative damage to DNA and proteins, leading to mutations and further instability.

• Chronic inflammation also disrupts the normal activity of epigenetic regulators, especially DNA methyltransferases (DNMTs).

  • DNMT1 maintains existing DNA methylation patterns, while DNMT3A and DNMT3B are responsible for de novo methylation (adding methyl groups to previously unmethylated DNA).

• Inflammation-induced ROS and cytokines, combined with cGAS-STING pathway activity, can dysregulate these DNMTs, leading to aberrant DNA methylation.

CpG Island Hypermethylation

• CpG islands are regions of DNA rich in cytosine (C) and guanine (G) dinucleotides. They are commonly found in the promoter regions of genes, especially tumor suppressor genes and other regulatory elements.

• DNA methylation at CpG islands involves adding a methyl group (-CH3) to the cytosine residue, typically silencing gene expression.

• In the context of chronic inflammation and cGAS-STING activation, DNMTs can become overactive or improperly regulated, leading to hypermethylation of CpG islands.

  • Hypermethylation of promoter CpG islands can silence tumor suppressor genes such as p53, RB1, BRCA1, CDKN2A, or PTEN.

  • This gene silencing prevents these proteins from performing their normal roles in controlling the cell cycle, promoting apoptosis (programmed cell death), and repairing damaged DNA.

APOBEC-Induced Mutations and Cancer

• APOBEC enzymes, particularly APOBEC3B, are often upregulated in cancers and can cause C-to-T or C-to-G mutations.

• These mutations accumulate in the genome, promoting genomic instability. This, coupled with the silencing of tumor suppressor genes through CpG island hypermethylation, creates an environment conducive to tumorigenesis.

• Cancer types where the APOBEC mutational signature is prevalent include breast cancer, lung cancer, bladder cancer, and others.

Autoimmune Disease Mechanism

• Chronic cGAS-STING pathway activation can lead to autoimmune diseases by promoting the constant production of type I interferons (IFN-a, IFN-b) and proinflammatory cytokines (IL-6, TNF-a).

• This hyperactive immune response can lead to autoimmunity because the body begins attacking its own cells and tissues.

• SLE (systemic lupus erythematosus) is a classic autoimmune disease associated with cGAS-STING overactivation. In lupus, there is excessive recognition of self-DNA, driving a hyperinflammatory state.

• APOBEC-induced mutations can also alter the antigenic profile of cells, which may promote autoimmune reactions as the immune system mistakenly identifies altered self-cells as foreign.

Macrophage Activation and Inflammatory Disease

• Macrophages are immune cells that respond strongly to cGAS-STING activation. When activated by STING, macrophages produce high levels of proinflammatory cytokines like TNF-a, IL-6, and IL-1b.

• Chronic macrophage activation can lead to tissue damage and contribute to autoimmune diseases or hyperinflammatory syndromes, such as macrophage activation syndrome (MAS).

  • In diseases like Adult-onset Still’s disease (AOSD), macrophage hyperactivation driven by the cGAS-STING pathway results in widespread inflammation.

  • Overactive macrophages in the context of chronic inflammation can perpetuate disease progression by continuously driving inflammatory signals and promoting tissue destruction.

Disease Outcomes

• Cancer: The combined effects of APOBEC-induced mutagenesis and CpG island hypermethylation promote cancer development by driving genomic instability, silencing tumor suppressor genes, and activating oncogenes.

• Autoimmune Diseases: Chronic activation of the cGAS-STING pathway leads to autoimmune disorders like SLE by generating self-DNA recognition, continuous type I interferon production, and inappropriate immune responses.

• Hyperinflammatory Syndromes: Macrophage hyperactivation, resulting from STING signaling, can lead to hyperinflammatory conditions like MAS, AOSD, and other autoimmune or inflammatory diseases.

Summary of the Detailed Pathway:

1. DNA plasmids enter the cytoplasm, activating cGAS.

2. cGAS produces cGAMP, activating STING.

3. STING triggers immune signaling through TBK1, NF-kB, and IRF3, leading to the production of cytokines and interferons.

4. APOBEC enzymes are activated and induce cytosine deamination, causing C→T or C→G mutations in DNA.

5. Chronic inflammation and ROS production disrupt DNMT function, leading to hypermethylation of CpG islands.

6. Hypermethylation silences tumor suppressor genes, while APOBEC mutations contribute to genomic instability, driving cancer.

7. Chronic STING activation drives autoimmune diseases through continuous type I interferon production.

Macrophage hyperactivation results in hyperinflammatory syndromes like MAS and AOSD.

If we pull this into a short highlighted cliff notes section:

DNA plasmids enter the cytoplasm, activating cGAS.

cGAS produces cGAMP, activating STING.

STING triggers immune signaling through TBK1, NF-κB, and IRF3, leading to the production of cytokines and interferons.

APOBEC enzymes are activated and induce cytosine deamination, causing C→T or C→G mutations in DNA.

Chronic inflammation and ROS production disrupt DNMT function, leading to hypermethylation of CpG islands.

Hypermethylation silences tumor suppressor genes, while APOBEC mutations contribute to genomic instability, driving cancer. This can also drive autoimmune states.

Chronic STING activation drives autoimmune diseases through continuous type I interferon production.

Macrophage hyperactivation results in hyperinflammatory syndromes like MAS and AOSD

These tests could be used to quantify any type of medication injury, any drug injury, not just things with modified RNA in them, or DNA plasmids, or spike protein. You could use a test system like this (of course there is more lab work demanded—this is just highlights, which feels wild to say, considering the length of this, you could run these tests on someone who was injured by attenuated vaccines. You could run these types of tests checking methylation status on those who got Remdesvir—the sky is really the limit on running this type of test.

The first study mentioned—it was tracked that those with a significant immune system response lost a couple of years of their life. YEARS.

What happens to those with injuries? What happens to those who had serious infections AND injuries?

These are the questions that need to be answered.

Sources:
pmc.ncbi.nlm.nih.gov/articles/PMC9203887/… https://nature.com/articles/1205600… https://pubmed.ncbi.nlm.nih.gov/33979432/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10487967/