HomeDiscoverA Closer LookWhat Does The Science Say About COVID-19 Boosters and IgG4?

What Does The Science Say About COVID-19 Boosters and IgG4?

If you’ve been on the internet over the last year, you might have seen characters like Brett Weinstein claim that COVID-19 boosters are bad because of IgG4. But what is IgG4? Is it bad? Does it do what he says it does and are COVID boosters making us sick?

Firstly, I found no evidence that COVID-19 boosters are making COVID-19 infections worse. Quite the opposite! Secondly, some social media scientists seem to have got the wrong end of the stick about IgG4 and what it does.

Medical News Bulletin readers expect to see some science behind bold statements, so I’m going to walk you through:

I took a deep dive into the literature to get a better understanding of what is going on. It’s not absolutely clear cut, but what I did find was reassuring.

Feel free to tell us what you think and ask questions in the comments!

What Are IgGs?

IgGs are a sign of long-term immunity

IgG is a subtype of antibody. Different types of antibodies have distinct jobs in protecting us from pathogens and helping us to heal from injuries. IgG antibodies are very important in defending our bodies from viral, bacteria and yeast infections.

Antibodies have differing features and abilities. IgGs are very useful because they can penetrate almost all types of tissue in our body. They are relatively stable with a long half-life and they can recruit and activate several kinds of white blood cells that attack pathogens.

You might have seen IgG antibodies mentioned a lot in stories about long-term immunity to COVID-19. This is because immunologists use these antibodies as a marker to see how much our immune system has adapted to spot a particular pathogen.

Basically, if you have IgG antibodies against a virus it means that your immune system recognizes it and is ready to fight it off. High IgG levels mean that a vaccine programme is working. IgG antibodies develop when your immune system has seen a particular antigen (antigens are things that antibodies recognise and stick to, think a chunk of virus, bacteria, foreign object, even a weird protein on a cancerous cell) many times and knows that it needs to deal with it quickly.

IgGs help us fight off infection

Our bodies use IgGs to control the inflammatory process. Inflammation is the body’s response to injury or infection. Blood flow to the area increases and tissue swells to allow white blood cells to get to the site and start the repair job. This could involve cells that eat and remove debris and microbes, cells that kill infected cells, cells that attack parasites and microbes, cells that lay down materials to patch up damage.

Inflammation can be useful to help us heal, but if the reaction is too big or goes on too long it can do more harm than good. Remember the early days of COVID-19 when people were absolutely pole-axed by the powerful immune response to the new virus? These days we see that less often because our immune systems know what it is and that they don’t have to throw everything they have at it. That’s down to IgGs.

IgGs Keep Inflammation Under Control

IgGs are important in helping our bodies to heal and fight off bugs. We use IgGs floating around in our body to detect microbial invaders and send out the alert to patrolling immune cells to come and help. People who lack IgGs are more likely to develop autoimmune reactions and some researchers believe that IgGs are important in switching off and damping down an autoimmune response.

However, IgGs also have a dark side. There is some evidence to suggest that they are the culprits in some autoimmune diseases. IgGs can contribute to autoimmune syndromes such as lupus by misidentifying our body’s own tissue as pathogens. Researchers are continuing to probe the role of IgGs in autoimmune disease to find out how they are involved and what can be done to modulate their activity.

What is IgG4?

IgG4 is a subtype of IgG antibody

IgG4 is one of the four types of IgG. It has a special role in helping us to deal with chronic infections. Our adaptive immune system makes IgG4 antibodies that specifically recognize things in our bodies that shouldn’t be there. This could be allergens, like pollen, parasites, microbes, viruses, etc. When you have been exposed to a potential pathogen for a long time, eventually some of your antibody making B-cells start making IgG4 in addition to other B-cells that make other types of more reactive antibody.

IgG4 antibodies are a special class of antibody that doesn’t trigger a strong immune response like the other members of the IgG family. These free-floating antibodies stick to their targets and stop them from infecting or bothering cells in your body. They block allergens and pathogens and gum them up instead of recruiting immune cells to mount an attack.

In this way, IgG4s help our bodies to trap and deal with allergens, proteins from bug bites or stings and chronic infections without triggering inflammation.

For example, when you breathe in SARS-CoV2 particles, IgG4s in the lining of your mouth, nose, throat and in your lungs will catch and neutralize the virus as a first line of defence.

IgG4 quietly swats pesky bugs

In its normal role, IgG4 damps down the immune response when it goes on too long and helps our immune system to stop responding as strongly to antigens to which we are repeatedly exposed. This means if your immune system keeps being exposed to a substance that triggers a reaction, after a while IgG4s will start to recognize them as an old acquaintance. Your immune system will deploy IgG4 to calm the reaction down before the inflammation does more harm than good.

When researchers say they saw less of a response by certain cell types (NK cells, phagocytes), it just means that the balance of defence mechanisms we used has tipped. The gentler-on-the-body IgG4 is being used to neutralize the threat instead of the all guns blazing cytokine reaction.

IgG4s helps us to avoid excessive immune responses to foods, parasites, certain medicines and even our own bodies when we have an autoimmune reaction. This could be the mechanism behind the idea of curing, or reducing the severity of allergens by giving people very low dose exposures over a long period of time. The idea is that the IgG antibody will neutralize the allergen before the more potent antibodies spot it and trigger a massive reaction. This approach has been successful in increasing tolerance of pet allergens and reducing the danger of peanut exposure.

IgG4 and immune disorders

There are a few rare illnesses that involve IgG4. People who don’t have enough IgG4 seem to suffer more from respiratory infections, yeast infections upset stomachs and allergies. When IgG4s misbehave they can trigger autoimmune disease, where they stick to our body’s own proteins and interfere with everyday cellular processes. Some cancers can trick IgG4s into thinking they are not so dangerous and preventing out anti-cancer T-cells from attacking. In some situations IgG4s can also glue up antibody-based drugs, believing they are preventing an allergic reaction.

IgG4 – Related Disease

IgG4 – RD occurs when our adaptive immune cells attack our own organs, causing them to become thicker and enlarged with fibrosis. These malfunctioning antibody-making B-cells, also start making IgG4 instead of the IgM or IgD antibodies they would usually make. Generally, researchers don’t believe that the IgG4 antibodies cause the damage as they are usually involved in calming immune responses.

IgG4s and COVID-19

Do COVID-19 vaccines trigger IgG4 production? Yes! And they are supposed to!

Should I be worried about IgG4?

Some people on popular social media sites have expressed concern that getting COVID-19 vaccine boosters every year is leading to people making IgG4s that recognize the SARS-CoV2 virus as an old friend and nothing to worry about.

These people claim that they are worried that getting vaccinated too often will make us less immune to COVID-19 because our bodies won’t realize it’s a harmful virus. They have also posited that IgG4-related disorders could be triggered. As we discussed before, IgG4 is unlikely to be the cause of IgG4-RD, it’s just the warning sign that something is wrong with the B-Cells.

What’s more it seems that they have fundamentally misunderstood how IgG4 works. IgG 4 can’t recruit immune cells or trigger a massive inflammatory response to clear the infection; instead it acts like fly paper, grabbing and gumming up the virus so that it can’t infect cells. IGg4 grabs the spike protein physically blocking the machinery that the virus uses to get into the cell.

IgG4 doesn’t hold back the rest of the immune system, saying to the virus, ‘have at it, nothing wrong here! Go about your business.’ Instead, it deals with the viral particles early on so that we don’t have to bring out the big guns until things get worse.

IgG4 and B-cells

High levels of IgG4 antibodies against a virus indicate that a person has been infected by it for a very long time. Or, that they have been infected so many times that the immune system recognizes it as something that’s inevitably going to show up.

Quite a few research groups have noticed that after a few boosters, people’s adaptive immune system started making more IgG4 antibodies. It looks like mRNA based vaccines have in some cases, increased the proportion of B-cells that make IgG4 after boosting. There is, however, no evidence as yet that this makes the immune system worse at dealing with COVID-19.

This shift in the balance of what types of antibodies the B-cells make might not even be such an unusual event. Because COVID-19 has been so widespread and so dangerous, scientists have applied far more intense scrutiny to how well the vaccines work and what happens to our immunity as time goes on. One thing we often forget is the more you look at something, the more quirks you notice. There are also far more people getting regular COVID boosters than other vaccines so it’s also a lot easier to study.

Does IgG4 hurt my immunity?

We know from the case of the German man who got 200 boosters in a year that the COVID-19 jabs did not trigger excessive IgG4 production. His immune system was recognizing Sars–CoV2 as a threat and attacking it just fine years later. That’s just one case, though. What does the literature say?

Firstly, we know that getting boosted against COVID-19 not only prevents severe cases of COVID-19 if you encounter the latest version of the virus, it also lowers your chances of developing long COVID or PASC.

There are countless epidemiological studies, case reports, investigations into different situations where they show boosters help build up COVID-19 fighting antibodies. I have had a hard time finding any research papers that show evidence that boosters make things worse.

I tried to find examples of Anti-SARS-CoV2 IgG4s causing problems without much luck.

IgG4 in the literature

So far I haven’t found any evidence that more IgG4 producing B-cells makes people less immune to COVID-19. In fact, these IgG4s are very good at grabbing and blocking the SARS-CoV2 viral particles.

I found a few research articles that noticed more IgG4 and less activity from some virus fighting immune cells. For example, researchers in Utrecht found that older adults (over 65 years) developed more IgG4 antibodies after getting boosted. They did not investigate whether this made COVID-19 infections worse, and they did not compare relative levels of antibodies, the authors themselves said it was hard to draw any conclusions. But we’d expect there to be IgG4 antibodies circulating as once we hit long-term, ongoing exposure to COVID spike proteins they are there to be the first line of defence.

Another study I found addressed how IgG4-RD patients fared during COVID19. This study didn’t say that the vaccines caused the illness or made people less immune to COVID. Rather they looked at people who had an immune disorder already and described how being sick with COVID made their pre-existing illness relapse.

Informed Decisions

It’s too early to tell whether a larger proportion of COVID-blocking IgG4-making B cells are harmful or makes much difference to immunity. If this is something you are worried about, it turns out that the effect is mostly from getting the same mRNA vaccine every time. There’s nothing stopping you from changing it up. These days there are multiple types of COVID-19 vaccine on the market.

Also as the COVID variants adapt and try to outsmart our immune system, the vaccine targets will change too. You might have a lot of IgG4 antibodies against the original COVID-19 strain, but new vaccines are teaching your immune system to recognize a different version every time.

At the end of the day, it’s not a zero sum game. Your adaptive immune system has an amazing ability to change and is constantly modifying its responses to pathogens. Challenging your immune system with vaccines is still the best way to protect yourself and the people around you who have less healthy immune systems to avoid becoming very ill from infectious diseases.

Right now, when it comes to vaccines, we are spoiled for choice!

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Joanna Mulvaney PhD
Joanna Mulvaney PhD
Joanna Mulvaney worked as a bench researcher for much of her career before transitioning to science communication. She completed a PhD in developmental biology focusing on cell signaling in cardiogenesis at the University of East Anglia, Norwich, UK, before moving on to study axial skeleton development and skeletal myogenesis at King’s College London and regeneration of auditory cells in the ear at University of California San Diego Medical School, USA and Sunnybrook Research Institute, Toronto, Canada. When it comes to scientific information, her philosophy is: make it simple, make it clear, make it useful.

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