Great article. I had reasons why I did not mention IgG4-RD (IgG4-related disease) and IgG4 in late stage cancer, in my latest article. Thank you for pointing out that IgG4-RD is unrelated to Covid vaccine findings, and late stage cancer is the horse that pulls the IgG4 cart, not the other way around.
I hope for more research into this topic.
Considering changing my name to IgG4or (just kidding)
It's important that we be careful in finding this one thing and go searching all around without showing consideration towards how things should tie together.
The IgG4-RD information is interesting, but so little is known about it aside from the fact that IgG4 is found (albeit even inconsistently, as in some cases IgG4-RD is assumed as a diagnosis even with low IgG4 levels on testing).
The Fc-Fc binding ability of IgG4 is pretty interesting but that even itself is complex and so that would require additional investigation as well, all things that should be looked at before we make assumptions, especially because we know that many people are already in a tense state.
Wait, would the G's be pronounced twice, and is the 4 pronounced like an "A"?? People need to know!
The only conclusions anyone should be jumping to is that the jabs are neither safe nor effective. In fact, they have proved to be downright lethal, IgG4 or not.
It's true that the mass vaccinations don't meet any of the criteria of either safe or effective, but the intent here is to at least show that we can't run with any idea without first taking time to assess the information.
So yes, the vaccines have a lot of serious issues. As it relates to IgG4? Let's find some more information before we start making assumptions.
Wonderful, thanks for this additional perspective on this antibody switch. I love the science - the substackers weighing in and discussing is how the scientific process works. 👍🏽
Thank you Nova! There was a lot that I wanted to include but I was just going to ramble on a lot more than I did here, and a lot of my thoughts got jumbled while writing and so I made do with what I could put down. I also didn't want to spend a few days on this after I did so with my microbiome post and still need the follow-ups for. 🤷♂️
I don't know as much about the immune system as you do. I think it's truly a skill to be able to talk about enough of the details to relay its complexity, but not lose people with too many detail. It's a skill to discern what needs to be said, and what doesn't need to be said, to get a point across. I think you did quite a good job "making do with what you could put down". 😊👍🏽
"I don't know as much about the immune system as you do."
Oh, boy! I say the same thing to Brian from Unglossed all the time! So what does this mean??
But jokes aside, I just have difficulties with anything biology related because a lot of it is rote memorization. Intuition doesn't tell you Photosystems II comes before Photosystems I, but that Photosystems I is named Photosystems I because it was discovered first! Then we have all of the T cells and all the CD whatever number plus they are! It lacks intuition and so I get confused very easily.
It's not the same as organic chemistry, where you can learn some of the basic ideas and start applying them, see why it doesn't work in certain situations and understand why that may not be the case. I find it far easier to intuit chemical processes more than biological.
I'm certainly still trying to find my groove in writing. I find that not many people read the studies that are cited, so when first writing I thought it important to just put the entire study in an article so that people can't avoid it that way, but of course that doesn't work all the time (or really any time!).
It's hard to not lose people because one never knows what level people are at with their knowledge of science, so I sort of compromise with a hope that I try to make the information accessible, and people spend a bit of time working and struggling through some of the finer details and so we can meet somewhere in the middle.
But unfortunately that doesn't tend to happen often, hence the what vs how to think, and so many people may just want a tl;dr and told what to think of a study.
Take a look at Brian's most recent post on that negative efficacy study, and see how many people are able to read the graph. Not many people spent time to figure out the graph, but they've made conclusions from it that aren't based on the information provided. 🤷♂️
Anyways, I had to stop my writing at some point. Substack keeps yelling at me my posts are too long! And on my recent microbiome post Substack was chugging along. I guess it was too much onscreen for Substack to deal with!
😄 you have a lot to say, that is great! Does substack have a word limit to each post?
I appreciate you are balancing what people can follow along with, and the importance of making them think. I think this is a needed evolution of the human population, the ability to think for themselves, as we've found out these past couple years. It can be hard when, like you say, you have a range of people reading your stack. I have a BS in biology, a minor in chemistry, and a masters in physical therapy, but I haven't used biology directly as a physical therapist. I created a cheat sheet of the immune system to help my learning as I'm reading all of these substacks. I wish I had you around during organic chemistry! 😵💫 I had to take it twice to pass, it's the first time I felt like I couldn't "get" something academically.
I have been really appreciating Brian's knowledge and perspective too! He's been invaluable. I interpreted that study as straightforward negative efficacy too, until Brian brought his perspective in, which made so much sense.
Funny, a comment brought me Della-Torre's study, probably from your post, and I dismissed it as 1) reflecting that IgG4 reflects comorbidities and 2) fabricating a group "trend" out of seven or so outliers https://unglossed.substack.com/p/incredible-tolerance-news/comment/11512500 . The reason for the 700 cutoff is that the high-IgG4 high-death outliers guarantee in advance an impressive graph. Milan is the birthing-ward of garbage studies.
That is true. The researchers never state what the antibodies were in relation to, so it's just as likely the high IgG4 may have been derived from something else, again being a bystander blamed for the crime I suppose.
My interpretation was more that indications of elevated IgG4 could possibly be related to immune dysfunction, as if to serve as a predictive marker that something is wrong with this person's immune system, which itself would depend upon many of its own factors.
It does appear that the 700 cutoff may have been chosen to meet statistical significance, so I'm thinking a bit of p-hacking may have caused them to choose that cutoff...
I think some are too quick to jump on the Fear Porn wagon.
What it does point to is just how poorly studied these vaccines are, or if this is known they don't feel inclined to let us know. Certainly needs a closer look with some people on their 3rd or 4th booster
Definitely in agreement about the lack of studies!
My initial comments when Brian posted this study was that they probably never looked into this because they probably never thought that boosting would be needed. Then the vaccines weren't as effective as they were made out to be, so the vaccine manufacturers scrambled to push out studies looking at how many antibodies are sticking to the spike, but they didn't spend time looking at what antibodies were being produced.
The Bivalent would be interesting, but Brian posted an article suggesting some sort of imprinting (not in the typical sense), in that those who got Wuhan-specific vaccines produce Omicron-specific antibodies, yet those who got infected with Omicron don't produce Wuhan-specific antibodies, which is rather weird.
I wouldn’t be too quick to excuse these guys. This is a well established phenomenon
“Long term exposure to antigens may result in antigen specific IgG4 production as was demonstrated in studies on prolonged exposure to antigens such as different allergens, Factor VIII and IFN-β”
Plus we have the unusual persistence of spike protein in the lymph nodes (60 days) according to a recent study which might enhance this. Although it remains to be seen how much of an effect it has on clinical outcomes
They have had over 2 1/2 years to document the bio distribution of spike, quantify how much is produced per dose and how long before spike is degraded or excreted, yet they are allowed to stay silent.
One take home from all this, clinical trials need to be designed , performed and evaluated by independent 3rd parties and appointed by someone other than the FDA or Mfr
"We elected to engineer G921 to benefit from the transcytosis and extended half-life potential of IgG4 Fc while eliminating binding to low-affinity FcγRs and thereby avoiding any likelihood of ADE of G921 that could theoretically occur with an IgG1 Fc fusion protein."
This makes me wonder if the shift to IgG4 after vaccination might be protecting people from ADE.
Thanks for the link! I'll try to take a look when I have the time.
Essentially, if IgG4 class shifting is occurring to some degree then it would contradict the ADE model. However, other IgGs are still being produced, but IgG4 itself lacks effector function and hypothetically shouldn't be able to engage in ADE.
Thank you Joomi! It's interesting to say the least, and as information comes out we should see what the significance of this is in relation to other diseases, but as of now it's sort of throwing a lot of fuel onto the fire.
Many people want answers, and so to offer answers rather than hold off and raise hesitancy can cause a lot of issues.
DrBeen did a reassuring video on the subject, although my main takeaway is ‘ does this mean the mRNA is hanging around long enough to be continually stimulating the immune response such that it converts more to IgG4’?
Interesting, thanks! I'll take a look when I have the time.
I think Dr. Mobeen tends to do an earnest job, however there have been a few times where his assessment didn't seem proper. I'll see how he takes a look at this study when I can.
The issue with mRNA hanging around is that mRNA hanging around doesn't inherently mean that spike is still being produced. It's similar to how PCR serves as a proxy for infection, but one PCR test doesn't tell us if the virus is still infectious.
So mRNA can still be found but may be inert, aside from possible inflammation which can have its own issues.
IgG4 at least suggests possible spike lingering, and I believe a few studies have noted spike for around several weeks. So it may be a high dose spike that persists for longer than was originally assumed that may be at play, and if that's the case it's another reason why studies are needed to see how long both mRNA and spike last.
"This is important to highlight, because when we look at studies it’s easy to look at the presence of IgG4 and immediately infer that the IgG4 is the cause of the maladies."
Yes, and I'm glad you mentioned it. I was thinking about bringing this up in connection with viruses and the gut microbiome, but I am still digesting that post (pun intended). I'll wait, and comment after finishing the article.
We could very well find that IgG4-RD is being caused by the vaccines, but to that effect we would need more information. Because of that lack of information I wanted to attenuate some of the excitement (fear more like it to be honest....) around IgG4.
A problem with this thinking is one that has generally plagued COVID discourse, in that it takes highly complex ideas, of which much is unknown, and attempts to boil it down in order to provide people with answers.
This process of showing people what to think, rather than how to think means that many people will sop up information and use it as they are being told to, without so much as thinking of the underlying mechanisms or how to piece information together into a broader concept.
I'm not sure what you are getting at Patricia. It may be true of all medical fields, but it doesn't mean that we follow those same ways of thinking because others do.
My idea here was to point out that we're dealing with a ton of uncertainty, and rather make definitive statements in a sea of uncertainty we should figure out what bits of uncertainty can be made more certain, what pieces of greater certainty can be tied together, and then we can use consilience and see what direction all of this information points towards.
I did skim a bit, but one huge issue I didn't see you addressing, is that this lowering of 3 and raising of 4 only occurs with the mRNA injections, not the vectored type such as AstraZeneca.
If nothing else that absolutely does implicate the shots.
My argument was never that this class shifting was not occurring, but that we don't know what IgG4 means with respect to other diseases, and how IgG4 from the spike is being tied to the uptick and pathology of other diseases.
Put another way, I am raising hesitancy to comments that the IgG4 from the vaccines mean that people will get super cancer, because we don't have much information to go off of.
Now, as it relates to the vector of vaccination I intended to make a comment about further studies where a comparison has to be made to Moderna's vaccines to see the extent of the IgG4 production from that. If we see a much greater level of class shifting there then we could argue that there is a dose-dependent relationship here, and that Moderna vaccinees may see a higher level of IgG4.
Well, in order to answer the diseases you sort of ironically need to know what the disease is, or at least the antigen. It's one of the issues with IgG4-RD, in that most researchers aren't sure what the antigen is that is causing the IgG4 production, it's just assumed that it's something that it's some antigen that exists within a person's body. It's assumed that it's an autoantigen (one of the body's own antigens, and therefore the targeting of it would be some sort of autoimmune disease), but still researchers are unsure as to what exact antigen.
In any case, it's believed that IgG4 is caused by persistent exposure to an antigen, whatever that antigen is. That means an allergen, a microbe, a pathogen, or a parasite. Helminths supposedly aid in the production of IgG4 as a way of obfuscate our immune systems, however in that context IgG4 production may be seen as a beneficial factor due to this anti-inflammatory/immunomodulatory mechanism, and helminths may ironically be a reason for the high rates of allergies in the WEIRD world due to our lack of parasites.
So IgG4 being bad or good depends on what is causing the production. For allergens, it's good for attenuating the allergic, inflammatory response. For cancer, it's bad because it may aid in tumor progression.
For viruses, the IgG4 depends on i's ability to still bind to the virus (avidity), the production of novel B cells that can produce other IgG's, and the balance between the two (among other things).
What the circulating study argues is that the IgG4 class switch has high avidity and low effector function, so they can still bind to the spike protein but they can't call to other cells to help eliminate the virus.
So what exactly does this mean for the virus? On the surface (no pun intended) if many antibodies are switching over to IgG4 they've essentially been relegated to monoclonal antibody status in my opinion. Most monoclonal antibodies are designed with modified or removed effector function, and so you can sort of think of IgG4 antibodies as having Sotrovimab, Regeneron, etc. floating around IF they can still bind to the spike.
Now, the question becomes what will happen if one is to be introduced to the virus, and what antibodies will be produced.
This is where proponents/opponents of OAS (original antigenic sin) will differ, as proponents of OAS will argue that the presentation of any spike will recall the mature B cells and have them release their IgG4 antibodies. Opponents of OAS will argue that one can still produce novel B cells that will make up subclasses outside of IgG4, and therefore it won't be a game of all IgG4 with no effector function.
This is sort of the conundrum right now, although I tend to lean towards the idea that novel responses can still be made. This also doesn't take into account that many people who get infected can still produce antibodies that target SARS-COV2's other antigens.
In order to test the extent of harm from as it relates to the vaccines, we would have to look at length since last dosage and number of infections to compare information, especially as we are in the era of Omicron with a rather distant spike protein and see IgG4 ratios relative to the other antigens. We would have to compare these to naturally infected individuals which no study dares to do, because you wouldn't really dare to be the "unvaccinated cohort" in a study.
But without that we don't even know the level of class shifting from repeat infection, so missing from all of these studies is a baseline, or at least a comparative profile of naturally immunized people.
We would also need a study comparing those who received Moderna and those who receive Pfizer. Most studies just utilize Pfizer, but because Moderna uses a higher dosage a comparison with those who got Moderna may tell us if this is a consequence of dosing. Again, we're missing data on that as well.
BUT EVEN WITH ALL THIS BEING SAID, the IgG4 class switching isn't the same for everyone, so it would be important to figure out why some people shuffle over real quick, and some people's immune systems aren't so brash to want to shift all into IgG4.
To this, a genetic or immunological profile may provide insights. As I stated, it could be that those who shift over to IgG4 quickly may actually have some sort of immunological dysfunction, and again the presence of IgG4 is not due to the vaccines as a whole but may be due to some immune dysfunction.
Note that obesity, chronic disease including autoimmune disease, the gut microbiome, nutrition, and sleep all factor into our immune systems, hence my comment above that there may be an association between the microbes in our gut and IgG4 production.
So we would essentially need to take a look at all of these factors in order to get closer to an answer.
But this is all my thoughts, and many people may have differing or far better thoughts out there, but hopefully this answers your questions!
I left a comment here already, but to answer your question to the best of my ability, IgG4 switch for Covid vaccine-related antibodies will mostly determine future reaction to COVID infections and to future vaccine doses.
There is no indication that it will affect cancers or cause the so-called "IgG4 disease".
Great article. I had reasons why I did not mention IgG4-RD (IgG4-related disease) and IgG4 in late stage cancer, in my latest article. Thank you for pointing out that IgG4-RD is unrelated to Covid vaccine findings, and late stage cancer is the horse that pulls the IgG4 cart, not the other way around.
I hope for more research into this topic.
Considering changing my name to IgG4or (just kidding)
It's important that we be careful in finding this one thing and go searching all around without showing consideration towards how things should tie together.
The IgG4-RD information is interesting, but so little is known about it aside from the fact that IgG4 is found (albeit even inconsistently, as in some cases IgG4-RD is assumed as a diagnosis even with low IgG4 levels on testing).
The Fc-Fc binding ability of IgG4 is pretty interesting but that even itself is complex and so that would require additional investigation as well, all things that should be looked at before we make assumptions, especially because we know that many people are already in a tense state.
Wait, would the G's be pronounced twice, and is the 4 pronounced like an "A"?? People need to know!
How dare you! Study titles say IgG4 + bad thing! Must make post! STUDY TITLES!
Urge to clickbait, rising...
The only conclusions anyone should be jumping to is that the jabs are neither safe nor effective. In fact, they have proved to be downright lethal, IgG4 or not.
It's true that the mass vaccinations don't meet any of the criteria of either safe or effective, but the intent here is to at least show that we can't run with any idea without first taking time to assess the information.
So yes, the vaccines have a lot of serious issues. As it relates to IgG4? Let's find some more information before we start making assumptions.
In sum: nobody knows. Just like comments on UFOs - no proof, no valid confirmation of any kind. We know NOTHING. So much for trusting the science.
Wonderful, thanks for this additional perspective on this antibody switch. I love the science - the substackers weighing in and discussing is how the scientific process works. 👍🏽
Thank you Nova! There was a lot that I wanted to include but I was just going to ramble on a lot more than I did here, and a lot of my thoughts got jumbled while writing and so I made do with what I could put down. I also didn't want to spend a few days on this after I did so with my microbiome post and still need the follow-ups for. 🤷♂️
I don't know as much about the immune system as you do. I think it's truly a skill to be able to talk about enough of the details to relay its complexity, but not lose people with too many detail. It's a skill to discern what needs to be said, and what doesn't need to be said, to get a point across. I think you did quite a good job "making do with what you could put down". 😊👍🏽
"I don't know as much about the immune system as you do."
Oh, boy! I say the same thing to Brian from Unglossed all the time! So what does this mean??
But jokes aside, I just have difficulties with anything biology related because a lot of it is rote memorization. Intuition doesn't tell you Photosystems II comes before Photosystems I, but that Photosystems I is named Photosystems I because it was discovered first! Then we have all of the T cells and all the CD whatever number plus they are! It lacks intuition and so I get confused very easily.
It's not the same as organic chemistry, where you can learn some of the basic ideas and start applying them, see why it doesn't work in certain situations and understand why that may not be the case. I find it far easier to intuit chemical processes more than biological.
I'm certainly still trying to find my groove in writing. I find that not many people read the studies that are cited, so when first writing I thought it important to just put the entire study in an article so that people can't avoid it that way, but of course that doesn't work all the time (or really any time!).
It's hard to not lose people because one never knows what level people are at with their knowledge of science, so I sort of compromise with a hope that I try to make the information accessible, and people spend a bit of time working and struggling through some of the finer details and so we can meet somewhere in the middle.
But unfortunately that doesn't tend to happen often, hence the what vs how to think, and so many people may just want a tl;dr and told what to think of a study.
Take a look at Brian's most recent post on that negative efficacy study, and see how many people are able to read the graph. Not many people spent time to figure out the graph, but they've made conclusions from it that aren't based on the information provided. 🤷♂️
Anyways, I had to stop my writing at some point. Substack keeps yelling at me my posts are too long! And on my recent microbiome post Substack was chugging along. I guess it was too much onscreen for Substack to deal with!
😄 you have a lot to say, that is great! Does substack have a word limit to each post?
I appreciate you are balancing what people can follow along with, and the importance of making them think. I think this is a needed evolution of the human population, the ability to think for themselves, as we've found out these past couple years. It can be hard when, like you say, you have a range of people reading your stack. I have a BS in biology, a minor in chemistry, and a masters in physical therapy, but I haven't used biology directly as a physical therapist. I created a cheat sheet of the immune system to help my learning as I'm reading all of these substacks. I wish I had you around during organic chemistry! 😵💫 I had to take it twice to pass, it's the first time I felt like I couldn't "get" something academically.
I have been really appreciating Brian's knowledge and perspective too! He's been invaluable. I interpreted that study as straightforward negative efficacy too, until Brian brought his perspective in, which made so much sense.
Funny, a comment brought me Della-Torre's study, probably from your post, and I dismissed it as 1) reflecting that IgG4 reflects comorbidities and 2) fabricating a group "trend" out of seven or so outliers https://unglossed.substack.com/p/incredible-tolerance-news/comment/11512500 . The reason for the 700 cutoff is that the high-IgG4 high-death outliers guarantee in advance an impressive graph. Milan is the birthing-ward of garbage studies.
That is true. The researchers never state what the antibodies were in relation to, so it's just as likely the high IgG4 may have been derived from something else, again being a bystander blamed for the crime I suppose.
My interpretation was more that indications of elevated IgG4 could possibly be related to immune dysfunction, as if to serve as a predictive marker that something is wrong with this person's immune system, which itself would depend upon many of its own factors.
It does appear that the 700 cutoff may have been chosen to meet statistical significance, so I'm thinking a bit of p-hacking may have caused them to choose that cutoff...
I think some are too quick to jump on the Fear Porn wagon.
What it does point to is just how poorly studied these vaccines are, or if this is known they don't feel inclined to let us know. Certainly needs a closer look with some people on their 3rd or 4th booster
Anyways, thanks for the balanced post.
Definitely in agreement about the lack of studies!
My initial comments when Brian posted this study was that they probably never looked into this because they probably never thought that boosting would be needed. Then the vaccines weren't as effective as they were made out to be, so the vaccine manufacturers scrambled to push out studies looking at how many antibodies are sticking to the spike, but they didn't spend time looking at what antibodies were being produced.
The Bivalent would be interesting, but Brian posted an article suggesting some sort of imprinting (not in the typical sense), in that those who got Wuhan-specific vaccines produce Omicron-specific antibodies, yet those who got infected with Omicron don't produce Wuhan-specific antibodies, which is rather weird.
I wouldn’t be too quick to excuse these guys. This is a well established phenomenon
“Long term exposure to antigens may result in antigen specific IgG4 production as was demonstrated in studies on prolonged exposure to antigens such as different allergens, Factor VIII and IFN-β”
https://pubmed.ncbi.nlm.nih.gov/22622790/
Plus we have the unusual persistence of spike protein in the lymph nodes (60 days) according to a recent study which might enhance this. Although it remains to be seen how much of an effect it has on clinical outcomes
They have had over 2 1/2 years to document the bio distribution of spike, quantify how much is produced per dose and how long before spike is degraded or excreted, yet they are allowed to stay silent.
One take home from all this, clinical trials need to be designed , performed and evaluated by independent 3rd parties and appointed by someone other than the FDA or Mfr
Great analysis; thank you for writing it!
Interestingly, the fc domain of IgG4 has been used to create a therapeutic by fusing it to ACE2 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438944/]. The authors described their rationale as follows:
"We elected to engineer G921 to benefit from the transcytosis and extended half-life potential of IgG4 Fc while eliminating binding to low-affinity FcγRs and thereby avoiding any likelihood of ADE of G921 that could theoretically occur with an IgG1 Fc fusion protein."
This makes me wonder if the shift to IgG4 after vaccination might be protecting people from ADE.
Thanks for the link! I'll try to take a look when I have the time.
Essentially, if IgG4 class shifting is occurring to some degree then it would contradict the ADE model. However, other IgGs are still being produced, but IgG4 itself lacks effector function and hypothetically shouldn't be able to engage in ADE.
But I'll try to take a look when possible.
Great article. I really appreciate that you took a nuanced approach to this topic... Agree that some are jumping to conclusions too quickly on it.
Thank you Joomi! It's interesting to say the least, and as information comes out we should see what the significance of this is in relation to other diseases, but as of now it's sort of throwing a lot of fuel onto the fire.
Many people want answers, and so to offer answers rather than hold off and raise hesitancy can cause a lot of issues.
https://youtu.be/bt8fcZmBVQw
DrBeen did a reassuring video on the subject, although my main takeaway is ‘ does this mean the mRNA is hanging around long enough to be continually stimulating the immune response such that it converts more to IgG4’?
Interesting, thanks! I'll take a look when I have the time.
I think Dr. Mobeen tends to do an earnest job, however there have been a few times where his assessment didn't seem proper. I'll see how he takes a look at this study when I can.
The issue with mRNA hanging around is that mRNA hanging around doesn't inherently mean that spike is still being produced. It's similar to how PCR serves as a proxy for infection, but one PCR test doesn't tell us if the virus is still infectious.
So mRNA can still be found but may be inert, aside from possible inflammation which can have its own issues.
IgG4 at least suggests possible spike lingering, and I believe a few studies have noted spike for around several weeks. So it may be a high dose spike that persists for longer than was originally assumed that may be at play, and if that's the case it's another reason why studies are needed to see how long both mRNA and spike last.
Excellent article. Thanks.
"This is important to highlight, because when we look at studies it’s easy to look at the presence of IgG4 and immediately infer that the IgG4 is the cause of the maladies."
Yes, and I'm glad you mentioned it. I was thinking about bringing this up in connection with viruses and the gut microbiome, but I am still digesting that post (pun intended). I'll wait, and comment after finishing the article.
We could very well find that IgG4-RD is being caused by the vaccines, but to that effect we would need more information. Because of that lack of information I wanted to attenuate some of the excitement (fear more like it to be honest....) around IgG4.
A problem with this thinking is one that has generally plagued COVID discourse, in that it takes highly complex ideas, of which much is unknown, and attempts to boil it down in order to provide people with answers.
This process of showing people what to think, rather than how to think means that many people will sop up information and use it as they are being told to, without so much as thinking of the underlying mechanisms or how to piece information together into a broader concept.
This is all medical fields
I'm not sure what you are getting at Patricia. It may be true of all medical fields, but it doesn't mean that we follow those same ways of thinking because others do.
My idea here was to point out that we're dealing with a ton of uncertainty, and rather make definitive statements in a sea of uncertainty we should figure out what bits of uncertainty can be made more certain, what pieces of greater certainty can be tied together, and then we can use consilience and see what direction all of this information points towards.
I did skim a bit, but one huge issue I didn't see you addressing, is that this lowering of 3 and raising of 4 only occurs with the mRNA injections, not the vectored type such as AstraZeneca.
If nothing else that absolutely does implicate the shots.
My argument was never that this class shifting was not occurring, but that we don't know what IgG4 means with respect to other diseases, and how IgG4 from the spike is being tied to the uptick and pathology of other diseases.
Put another way, I am raising hesitancy to comments that the IgG4 from the vaccines mean that people will get super cancer, because we don't have much information to go off of.
Now, as it relates to the vector of vaccination I intended to make a comment about further studies where a comparison has to be made to Moderna's vaccines to see the extent of the IgG4 production from that. If we see a much greater level of class shifting there then we could argue that there is a dose-dependent relationship here, and that Moderna vaccinees may see a higher level of IgG4.
Correct that IgG4 doesn't initiate cancers, but the DSBs from class switching commensurate with low levels of p53 and BRCA1 is a poor combination.
And non specificity is another problem regarding immunosuppression.
The theory and research is there, let's hope the clinical presentation doesn't follow. Too often it does for some unfortunate individuals.
https://doorlesscarp953.substack.com/p/spike-protein-inc-vax-induced-immunodeficiency-819
Well, in order to answer the diseases you sort of ironically need to know what the disease is, or at least the antigen. It's one of the issues with IgG4-RD, in that most researchers aren't sure what the antigen is that is causing the IgG4 production, it's just assumed that it's something that it's some antigen that exists within a person's body. It's assumed that it's an autoantigen (one of the body's own antigens, and therefore the targeting of it would be some sort of autoimmune disease), but still researchers are unsure as to what exact antigen.
In any case, it's believed that IgG4 is caused by persistent exposure to an antigen, whatever that antigen is. That means an allergen, a microbe, a pathogen, or a parasite. Helminths supposedly aid in the production of IgG4 as a way of obfuscate our immune systems, however in that context IgG4 production may be seen as a beneficial factor due to this anti-inflammatory/immunomodulatory mechanism, and helminths may ironically be a reason for the high rates of allergies in the WEIRD world due to our lack of parasites.
So IgG4 being bad or good depends on what is causing the production. For allergens, it's good for attenuating the allergic, inflammatory response. For cancer, it's bad because it may aid in tumor progression.
For viruses, the IgG4 depends on i's ability to still bind to the virus (avidity), the production of novel B cells that can produce other IgG's, and the balance between the two (among other things).
What the circulating study argues is that the IgG4 class switch has high avidity and low effector function, so they can still bind to the spike protein but they can't call to other cells to help eliminate the virus.
So what exactly does this mean for the virus? On the surface (no pun intended) if many antibodies are switching over to IgG4 they've essentially been relegated to monoclonal antibody status in my opinion. Most monoclonal antibodies are designed with modified or removed effector function, and so you can sort of think of IgG4 antibodies as having Sotrovimab, Regeneron, etc. floating around IF they can still bind to the spike.
Now, the question becomes what will happen if one is to be introduced to the virus, and what antibodies will be produced.
This is where proponents/opponents of OAS (original antigenic sin) will differ, as proponents of OAS will argue that the presentation of any spike will recall the mature B cells and have them release their IgG4 antibodies. Opponents of OAS will argue that one can still produce novel B cells that will make up subclasses outside of IgG4, and therefore it won't be a game of all IgG4 with no effector function.
This is sort of the conundrum right now, although I tend to lean towards the idea that novel responses can still be made. This also doesn't take into account that many people who get infected can still produce antibodies that target SARS-COV2's other antigens.
In order to test the extent of harm from as it relates to the vaccines, we would have to look at length since last dosage and number of infections to compare information, especially as we are in the era of Omicron with a rather distant spike protein and see IgG4 ratios relative to the other antigens. We would have to compare these to naturally infected individuals which no study dares to do, because you wouldn't really dare to be the "unvaccinated cohort" in a study.
But without that we don't even know the level of class shifting from repeat infection, so missing from all of these studies is a baseline, or at least a comparative profile of naturally immunized people.
We would also need a study comparing those who received Moderna and those who receive Pfizer. Most studies just utilize Pfizer, but because Moderna uses a higher dosage a comparison with those who got Moderna may tell us if this is a consequence of dosing. Again, we're missing data on that as well.
BUT EVEN WITH ALL THIS BEING SAID, the IgG4 class switching isn't the same for everyone, so it would be important to figure out why some people shuffle over real quick, and some people's immune systems aren't so brash to want to shift all into IgG4.
To this, a genetic or immunological profile may provide insights. As I stated, it could be that those who shift over to IgG4 quickly may actually have some sort of immunological dysfunction, and again the presence of IgG4 is not due to the vaccines as a whole but may be due to some immune dysfunction.
Note that obesity, chronic disease including autoimmune disease, the gut microbiome, nutrition, and sleep all factor into our immune systems, hence my comment above that there may be an association between the microbes in our gut and IgG4 production.
So we would essentially need to take a look at all of these factors in order to get closer to an answer.
But this is all my thoughts, and many people may have differing or far better thoughts out there, but hopefully this answers your questions!
I would love to volunteer as unvaxxed! Proud of it 💪🏻
I left a comment here already, but to answer your question to the best of my ability, IgG4 switch for Covid vaccine-related antibodies will mostly determine future reaction to COVID infections and to future vaccine doses.
There is no indication that it will affect cancers or cause the so-called "IgG4 disease".
That's my understanding anyway.