The New IgG4 Study Doesn't Say What Anti-Vaxxers Think It Does

Higher IgG4 could be a necessary, appropriate response.

Photo by ANIRUDH on Unsplash

There’s been some disturbing developments with Covid lately. First, the public is finally catching on to the rise in sudden deaths around the world. It sounds a little alarmist to say healthy people are dropping dead, but it’s happening. Second, a new study in Science Immunology shows that mRNA vaccines are having an unintended impact on our immune systems.

Both developments are leading to a resurgence in the anti-vaxxer movement, and it’s doing a lot of damage to public health.

Basically, anti-vaxxers are taking advantage of mistakes by the CDC and other public health officials. Those mistakes are turning into epic failures as they continue to dodge and deny their way through problems rather than address them. That leaves the public vulnerable to misinformation.

In short:

• Vaccines aren’t causing sudden deaths.

• Covid is causing sudden deaths.

• Vaccines aren’t ruining your immune system.

• Covid hurts your immune system.

• You’re better off vaxxed and boosted.

• Higher levels of IgG4 antibodies could be good.

• We still need mitigations (N95 masks, HEPA, etc).

• The CDC has done a poor job explaining this.

• Anti-vaxxers aren’t your friend.

First, a new wave of anti-vaxxer content has been attributing excess and sudden deaths to vaccines, which isn’t true. We know Covid itself can cause heart failure and organ damage, even in vaccinated people with mild cases. That explains the rise in sudden deaths far better than other theories. It’s the most consistent answer, and it’s something doctors have been saying for at least a year now. Unfortunately, the CDC and Coronavirus Task Force have largely ignored these findings, and that’s playing really well to the anti-vaxxer agenda.

The second problem is complicated.

According to a new study in Science Immunology, the Pfizer vaccines are driving up IgG4 antibodies. What does that mean?

I’m going to front-load my take: IgG4 antibodies could be playing a role in controlling inflammation during Covid infections and mopping up viral fragments after you recover from the acute stages of Covid. They’re not a sign that the mRNA vaccines have damaged your immune system.

The anti-vaxxers are jumping to conclusions.

All right, let’s go:

Your body makes 4 types of IgG (immunoglobulin G) antibodies. Those are the ones that do your immune system’s heavy lifting during infections. Most of your antibodies are IgG1. You can think of them as your immune system’s main infantry. Your IgG2 antibodies mainly deal with bacteria, and your IgG3 antibodies are basically super soldiers. Your IgG4 antibodies normally account for about 4-5 percent of your total immunoglobulins. These antibodies direct your response to things like allergens and irritants, not pathogens.

Scientists describe IgG4 antibodies as general antigen “garbage disposals” and have seen them play a role in helping your body build up a tolerance to things you’re regularly exposed to, even venom. For example: According to an article in The Journal of Allergy and Clinical Immunology, beekeepers have elevated IgG4 antibodies that reduce the effect of stings. A garbage disposal would be a very good way to get rid of viral fragments, wouldn’t it?

We know higher levels of IgG4 antibodies occur in people with IgG4-RD (IgG4-Related Disease), which looks a lot like autoimmune diseases and Long Covid. Anti-vaxxers jump on this as evidence that higher IgG4 levels are a bad thing. It’s not. A study in the Central-European Journal of Immunology shows that elevated IgG4 doesn’t cause IgG4 related-disease.

Instead, these antibodies probably “play a regularity function in the inflammatory process…which is more consistent with [their] natural properties.” So, we could infer that higher IgG4 antibodies are a good thing. They could be helping regulate long-term symptoms associated with Long Covid.

Anti-vaxxers don’t talk about that, though.

It doesn’t fit their narrative.

A 2021 study in the European Journal of Internal Medicine shows that a higher level of IgG4 antibodies “predicts a poor Covid-19 outcome.” This sub-class of antibodies doesn’t do a great job of neutralizing Covid compared to IgG1 and IgG3 antibodies. Well, no kidding. They’re designed to handle allergens and bee stings, not SARS itself. Scientists don’t know exactly why elevated IgG4 predicts poorer outcomes. It’s just associated. Again, we could infer that IgG4 doesn’t cause a poorer Covid response. It could signal other conditions.

There’s another wrinkle…

The Pfizer vaccine also seems to be driving down IgG3 antibodies. Either that, or it’s just not boosting them as well. Let’s contextualize. Your immune system doesn’t usually have many IgG3 antibodies to begin with. According to Trends in Immunology, they play a key role in promoting “enhanced control or protection against a range of intracellular bacteria, parasites, and viruses.”

Another study in PLOS One confirms the importance of IgG3 in SARS-2 neutralization. You can think of them as your special forces. They’re the Jason Bourne of antibodies. You don’t want too many dark ops assassins inside you either, but you need them for dangerous viruses.

This trend from IgG3 to IgG4 doesn’t look great on the surface. As the Science Immunology article states, “this class switch [from IgG3 to IgG4] was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition.” That’s a fancy way of saying the switch dampens your ability to destroy pathogens.

Sure, it’s unexpected.

On the other hand, maybe we shouldn’t expect IgG3 antibodies to remain high all the time after an infection. In some ways, it could make perfect sense for IgG3 to drop down and for IgG4 to amp up in order to control the exact kind of inflammatory responses we see with Long Covid.

We also know this trend isn’t just caused by vaccines. An August 2022 article in iScience shows that higher IgG4 levels happen after repeated infections. As the authors write, “The surprisingly higher prevalence of the IgG4 subtype might arise owing to repeated encounters with the antigen, which earlier studies on COVID-19 may not have captured.” We could be seeing a more mature response to the virus over time. It doesn’t matter whether you’re getting exposed to Covid spikes through infection or through mRNA. Either way, your immune system is responding with higher levels of IgG4 antibodies. I think most scientists would tell you vaccination is a much safer route than repeat infections.

Is that a good thing, or a bad thing?

Here’s a possibility:

We know some symptoms of Long Covid and Covid rebound are caused by “an overactive T cell response that is trying to eliminate all traces of the virus.” That was just recently published in an October 2022 issue of Clinical Infectious Diseases. The elevated IgG4 levels could simply mean that your body is trying to get your immune system under control. It could be helping.

Your immune system actually does need to ramp down after a serious viral infection, in order to let your body heal. As Harish Narasimhan at the University of Virginia writes in SciTech Daily, “your body dampens your immune system” during your recovery from Covid so that specialized stem cells can repair damaged organ tissue, in your lungs and elsewhere.

An overactive immune system can get in the way of your recovery, continuing to “produce tissue-damaging molecules long after the virus has been flushed out.” I mean, do you want a bunch of John Wick IgG3 antibodies running through you all the time, shooting at viral fragments?

I think you probably don’t.

Maybe after an acute Covid infection, it’s time for your IgG4 to take over for a while. Maybe they’re the mop-up crew that disposes of all the leftovers, just like they deal with allergens and bee stings. Maybe this is your immune system functioning the way it should. That’s what IgG4 antibodies do.

They’re your garbage disposal.

That makes sense to me…

There’s another final takeaway here. Even after you think you’ve recovered from Covid, you need to keep wearing an N95 mask while your body heals. You really don’t want to get sick with something else.

There’s a lot we don’t know about IgG4, but there’s nothing here that says vaccines are causing harm. There’s a need for more research, but this isn’t a reason to abandon mRNA vaccines yet. A great thread by Sabina Vohra-Miller says there’s nothing to be worried about. If anything, some of the evidence points toward it being a part of our recovery process we didn’t know about.

Higher IgG4 is a necessary, appropriate part of your immune response in some cases. All we know for now is that we need a better understanding of how IgG4 functions as our immune systems mature in response to Covid.

Meanwhile, we know:

• Getting Covid definitely isn’t good.

• It takes you a long time to recover, regardless of how severe it feels.

• N95 masks work.

• HEPA filters work.

• Even if you have a mild case, you should stay home.

• You should rest.

Bottom line:

Being vaccinated and boosted beats being unvaccinated by a wide margin. The anti-vaxxers will leap on any new study that might advance their case. They’ve been throwing spaghetti at the wall for years. Unfortunately, bad communication and poor leadership from the CDC have helped.

I don’t see western governments changing course anytime soon. Things are going to continue to deteriorate as healthcare workers quit or go on strike and medicine shortages get worse. It’s on us to stay informed and advocate where we can, and to make our own Covid-safe communities.

It’s all we can do.