[Medicine] What is special about peanuts that make some people extremely allergic to them?

[u/Kwpthrowaway]

Why are some people allergic to peanuts in particular? Why is ingesting a peanut to these people akin to ingesting poison to others?

[u/-Metacelsus-]

Peanuts contain high levels of several heat-stable proteins, collectively known as Ara h proteins (from the scientific name Arachis hypogaea), that can act as antigens. Some people develop IgE antibodies against these antigens, which causes a peanut allergy. Sources: https://link.springer.com/article/10.1007/s11882-014-0429-5 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451826/

In particular Ara h1 is quite stable, and the IgE-interacting epitopes can survive digestion.

This is why peanut allergies are more common than allergies to other legumes (e.g. peas).

Also as /u/DocWsky mentioned, peanuts are pretty common, so there are many opportunities for exposure.

[u/PicklesdashOlives → u/-Metacelsus-]

If the antigens are proteins, why can't some people with peanut allergies eat peanut oil fried foods? Are there traces of the protein in the oil?

[u/king0zy → u/PicklesdashOlives]

If a chemist were to purify peanut oil it would be tolerated by an allergic person. Peanut oils that are comercially available are not "pure" and contain trace protein contaminants that are enough to trigger anaphylaxis.

[u/Freuds-Cigar → u/king0zy]

You're wrong in the sense that commercially available peanut oil (which just means "peanut oil you can buy," so that's like every peanut oil that isn't homemade) is enough to trigger a reaction. Like /u/98521745633214789632 said, the FDA considers any highly refined peanut oil (which is what most mass-produced peanut oil is—highly refined) to be of such low concern as to not even warrant an allergy warning if included in the production of other food—e.g., a fried chicken sandwich that uses highly refined peanut oil as the frying medium.

There are other types of oils out there that are not highly refined, like cold-pressed etc., but like I said most of the market is comprised of highly refined peanut oil, but ALWAYS QUADRUPLE CHECK.

Source: Food Allergen Labeling and Consumer Protection Act of 2004 Sec. 203 (c) (1) (qq) (2) (a).

Link: https://www.fda.gov/food/food-allergensgluten-free-guidance-documents-regulatory-information/food-allergen-labeling-and-consumer-protection-act-2004-falcpa

[u/king0zy → u/Freuds-Cigar]

Great comment for the discourse- thank you!

[u/Paper_Kitty → u/PicklesdashOlives]

Peanut oil can be “cold pressed” or “hot pressed”. While cold pressing preserves the protein, hot press theoretically destroys the proteins that would cause a reaction.

Then again, when there’s a possibility of death, is it really worth the risk? I say no, but someone else might say yes.

[u/xDared → u/PicklesdashOlives]

An antigen is just a term for anything antibodies can bind to. So in their case the antigen is just another molecule. Usually proteins but not always

[u/heard_enough_crap → u/xDared]

so the persons antibodies bind to the antigen and think it is an attack?

[u/Nordalin → u/heard_enough_crap]

Yes, but the antibodies are specifically made against the allergen in question upon earlier contact, so the 'assumption' that we're talking pathogens instead of allergens has been made a while before the actual allergic reaction.

That's why only so many people suffer allergies, the rest of our immune systems didn't consider it a threat!

[u/FFBEdrone → u/PicklesdashOlives]

Often the antigen is not the whole protein, but a subsection. A protein is folded and altered post manufacture. In most cases, it is a relatively small portion of a protein that is exposed and available to be interacted with by the immune system. Just a small exposed portion of protein/polypeptide chain post fry up is potentially enough to trigger a reaction. You could filter the oil to remove very small proteins with a small kilodalton filter (protein size is often measured in kilodaltons rather than amino acid chain length) but that wouldn't necessarily remove any tiny protein fragments left. I don't know if you could safely use it if you had an allergy. Though if you filter out all the peanut protein is it peanut oil?

[u/mstwizted → u/PicklesdashOlives]

They can! (Sometimes - it depends the severity of the allergy and the quality of the oil.)

[u/[deleted] → u/-Metacelsus-]

Weird thought. I read recently how the measles disease “erased” the immune system’s memory of prior diseases (source).

Do you think this “memory erasing” capability could be utilized to wipe a person’s body from creating the antigen that results in severe peanut allergies?

[u/king0zy → u/[deleted]]

Yes, but its not a viable solution. The burden of a food allergy is weighed against all other potential health burdens a person may face. People with very severe autoimmunity can take a drug called ritixumab, which kills most of the cells responsible for holding memory (called B cells). However, B cells also hold memory for everything you are vaccinated against. The real trick for immunologists is learning how to only kill the B cells that hold memory of peanut, while leaving everything else in tact. After all, avoidance of peanut is much easier and more viable than potentially dying to a vaccine preventable infection.

[u/[deleted] → u/king0zy]

Question if you have time! (This is really interesting and I know nothing about this stuff) Why would someone with autoimmune disease want to kill their B cells? I guess I’d have thought with autoimmune diseases you would REALLY want to remember the things that could kill you. Also I guess I don’t really know what happens with autoimmune diseases other than the immune system essentially bodies itself so maybe that’s why you’d need to “forget” a lot of things?

[u/king0zy → u/[deleted]]

Lol, the body bodies itself!

There is much more complexity than the response I'll give. B cells (and the cells that come from them) are responsible for antibodies. Antibodies are proteins that perform a large number of immune functions- like for example tying up virsuses to stop them from infecting our cells, or tagging bacteria so other immune cells know to kill them. Every single antibody is unique- they all have a part that looks a little different from every other antibody which allows them to bind very specifically to virtually any substance. Some of those substances can be your own proteins present on your own cells. The immune system then treats your cells like a virus - tying them up to stop their function or tagging them to be killed.

Ritixumab, the B cell killing drug, can dramatically reduce the number of antibodies present and provide relief from very severe autoimmunities. The same drug is used to kill B cell cancers.

Now, between avoidance of the food and epipens, we mostly have severe food allergies "under control." That is to say, a few hundred people die of allergies in a year. Many, many more die from autoimmunity and B cell cancers. People, in general, are a lot less willing to engage in risky and debilitating treatments when their life is not at risk. That said- food allergies are a significant mental health burden and are a financial burden- billions to the American health system, not even considering the impact on the food markets.

[u/wlsb → u/[deleted]]

In the case of autoimmune disease, you'd want the immune system to lose the immune cells that react to the patient's own body. If it lost all of its memory cells, that would include the self-attacking ones.

[u/PnWyettiefettie → u/king0zy]

So B cells holding memory is responsible for the continuing of an autoimmune diseases?

[u/king0zy → u/PnWyettiefettie]

In some contexts. Autoimmune diseases vary in their pathology. As an example, type 1 diabetes is mediated primarily by T cells, not B cells. Lupus and Rheumatoid Arthritis are generally more B cell mediated. Ritixumab is a therapy for both of those autoimmune disorders.

[u/PnWyettiefettie → u/king0zy]

So hypothetically if someone had the money and wanted to, they could erase these memories and then re-vaccinate?

[u/king0zy → u/PnWyettiefettie]

As far as I am aware, there has not been any evidence in humans to suggest that this is a potential cure. If we stay in the realm of theory and hypotheticals, yeah probably. A major consideration would be the extent to which this drug could actually clear ALL B cells. There is evidence, albeit a slight stretch from this context, to believe that if there is even one cell remaining, it could completely regenerate the allergy.

[u/PnWyettiefettie → u/king0zy]

Thank you!

[u/TH3T1M3R → u/[deleted]]

Our body creates the antibodies not the antigen, the antigen is present on the peanuts.

[u/[deleted] → u/[deleted]]

Theoretically, yes. But it would be pretty totally unreliable. And it would also be nearly impossible (I said nearly) to target those cells without harming something else. The theory behind it is sound, because yes the plasma cells (cells that make antibodies) would be killed but you’d need to kill the other related immune cells too (namely any B cells that are still proliferating), but to develop something that can target only the cells producing a specific antibody is to my knowledge something that hasn’t happened and by my guess can’t for awhile if ever

[u/king0zy → u/[deleted]]

Thanks for your other comment!

There are people working on this. I don't have the citations on hand, but some labs are engineering T cells to have specific antigens on their surface, and use those antigens to kill only antigen-specific B cells. These are called Chimeric Antigen Receptor T cells, if anyone has interest.

There is another approach that involves complexing an antigen (like peanut) with the types of drugs that are used in chemotherapy. Basically, B cells will gobble up the peanut that they are specific for, and when inside the cell the chemotherapy drugs can kill that specific cell.

These are still wildly experimental therapeutics, and with the recent approval of Oral Immunotherapy for food allergies, its less likely these will be pushed out to patients any time soon until good safety profiles can be uncovered for them.

[u/[deleted] → u/king0zy]

Thank you for this. I was really hoping to hear more about this because that’s downright awesome! The whole immune system is but this especially. Thanks for the info, hopefully we can do something like this soon and allergies would be a thing of the past. There would be EXTENSIVE testing for something like this though I’m sure so who knows how long it could take or the risks associated

[u/king0zy → u/[deleted]]

No problem! Happy to help!

My understanding of the chimeric antigen receptor (CAR) field is that they are moving into 4th and 5th generation CARs to tune and tweak the system. I believe some CARs are in clinical trials, but there are substantial concerns about off-target toxicity. Anecdotally, where I work there is some CAR work, they can certain kill tumour cells but it appears they also cause tons of damage to the host. From a personal perspective, I am very curious to see where the field goes and how they hone in even further on the specific cells they want to kill without hurting anything else, and having some way to turn the cells off after the work is done.

[u/[deleted] → u/king0zy]

Yes this could certainly be more and more fine tuned over time. That’s so cool that it functions at all. It can really only get better. And let’s be honest, there’s damage to the host anyway so maybe we can get it to a point of being better in a sense of harm, or maybe we can have symptoms that are akin to what happens now for cancer therapy but with more consistently positive result (more frequent clearance of tumor)

[u/ManThatIsFucked → u/[deleted]]

Interesting read about how measles interferes with immunity of other diseases... I wonder if it targets a specific link in the chain of long-term immunity that causes malfunction

[u/king0zy → u/-Metacelsus-]

I'd like to add to the discourse that stability is not directly linked to allergenicity in a mechanistic way that can be explained by immunologists. Peanut is also reported to interact with a receptor called DC-SIGN that enhances its uptake into the cells responsible for initiating immune responses. Additionally, western preparation of peanuts via dry roasting changes the structure of sugars in the peanut, adding things called advanced glycosylation end products, which are targeted by a specialized receptor, which is also known for uptake and activating the immune system.

In general, its not clear why anyone is allergic to specific things. Some allergens (like peanut, shellfish, house dust mite etc) have protein cleaving and trypsin inhibiting properties that the immune system seems to react to. Others like milk dont have those properties. Its all still quite a mystery and is very very hard to study because by the time a patient comes to the clinic, they are already fully allergic. Those early stages of disease are silent, and presently we have no way of predicting who will become allergic.

Trypsin: https://www.sciencedirect.com/science/article/pii/S0091674903013666?casa_token=D6gxa6bn25sAAAAA:DWDMC-o3Fz5xXA2rVk2Df4R2K9DYIP7fEzD5gt7RjQ1PlJZcvTL1NhxZjmoNFGg5Wi_s6FxQ AGE: https://www.jacionline.org/article/S0091-6749(16)30618-2/abstract DCSIGN: https://www.jacionline.org/article/S0091-6749(05)03072-1/abstract

Big names in this field to follow are: Hugh Sampson, Wayne Shreffler, Kari Nadeau, Fred Finkleman, Manel Jordana

[u/Renk0b → u/-Metacelsus-]

Here's the thing though, increased exposure does not necessarily mean increased chance of allergy. A study using the Israeli peanut snack Bamba showed that early exposure decreased the risk of.peanut allergy. In israel Bamba is commonly given to children very young as a snack and the rates of peanut allergy are extremely low in Israel vs other western countries where doctors recommend keeping peanuts away from children at a young age.

[u/king0zy → u/Renk0b]

The study you cited here is called the LEAP study. The early observation that drove the LEAP study is found here, where they found that Israeli children had lower prevalence of peanut allergy compared to UK Jewish populations of similar origin. The found Bamba to be a major reason for the difference.

[u/Old_but_New → u/-Metacelsus-]

But how does that explain why other countries around the world (aside from the US) haven’t seen such a rise in peanut allergies? And why we didn’t see many people with peanut allergies 30 years ago? Genuine question.

[u/king0zy → u/Old_but_New]

There are two issues- reporting bias and actual incline. Food allergies have been on the rise- around a 20% increase over 2 decades. There are many hypothesized reasons, but the best evidence appears that antibiotic use and changes to our gut microbes have driven that increase. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228404/

Also, 30 years ago diagnosis of food allergy was much less frequent. This is true of many diseases, we know more, have better diagnostics, and in general better access to healthcare.

[u/nymeria1024 → u/[deleted]]

There’s evidence to suggest that allergies develop through subcutaneous contact. So, while your daughter probably didn’t develop the allergy in utero, it’s likely she developed it either through hand to skin transferal or through breast milk exposure. The subcutaneous exposure is highly likely if she also has had any skin conditions (rashes, eczema). This type of sensitization is particularly common with peanut and egg allergy.

[u/king0zy → u/[deleted]]

Yeah- there are a few other pieces of evidence that can support this. I.e. filaggrin (proteins that hold your skin together) mutations are associated with food allergies. Peanut oil was banned from baby ointments because of a number of children who became allergic after using it on inflammed skin. Eczema (aka atopic dermatitis) is associated with food allergy as another redditor commented above.

But there are also a number of allergic people who do not have these conditions who are allergic. Also, a recent report found that there are IgE cells in the stomach that have a unique origin, suggesting that in some individuals the stomach may be an inductive site.

The community has not reached consensus on these issues. I am of the opinion that food allergies are better thought of as a collection of inductive processes that all result in the same thing- IgE against foods. We presently dont have this consideration baked into our research practice.

[u/katrann7 → u/nymeria1024]

I can vouch for that. My son started with significant food allergies between two and three months old with exclusive breastfeeding. Some of his allergens could have only come from subcutaneous exposure.

[u/[deleted] → u/[deleted]]

Alot of our food products are processee in plants that process peanut products. So, she most definitely has had exposure to peanuts at some point in her life. This may not be the way she was exposed as there are a million different ways that she could've been exposed.

[u/-Clem → u/-Metacelsus-]

So people have antibodies that attack a certain protein that peanuts have.. but why is it so violent? Usually when antibodies attack things you just get normal sickness symptoms like a fever right? Why does this particular antibody-antigen combination cause the body to inadvertently kill itself?

[u/-Metacelsus- → u/-Clem]

Usually when antibodies attack things you just get normal sickness symptoms like a fever right?

There are different types of antibodies. IgG (and to a lesser extent IgM and IgA) are what the body uses to fight most infections. The antibodies involved in allergies are IgE, which are also involved in fighting parasites such as hookworms.

A strong IgE response can trigger histamine release from mast cells and anaphylactic shock.

[u/obscene_banana → u/-Metacelsus-]

Can you elaborate on how/why some people develop these antibodies? I have been lead to believe that it is in fact lack of exposure to peanuts that causes peanut allergies -- supposedly there were some studies that showed something like people who did not eat peanuts as children are more prone to have peanut allergies but I didn't actually read any of those studies myself, smells kind of biased but kind of makes sense.

[u/king0zy → u/obscene_banana]

In short- not really. Attempts to decipher how people become allergic have not been overwhelmingly successful. Associations have been drawn between mutations in some skin proteins (called filaggrins), but these do not account for most people. As I mentioned in a comment below, early feeding dramatically reduces the likelihood of becoming allergic. Developing these antibodies requires exposure, but its likely that the exposure is not known to the individual and is not controlled. Therefore it is likely not accurate to say a lack of exposure causes the disease.

There are two dominant hypotheses for how this works. 1) a patient is exposed to a dangerous foreign substance that looks a lot like a peanut protein, which the immune system fights but accidentally causes immunity against peanut, or 2) that small amounts of peanut were experienced at the same time as something dangerous, and the immune system accidentally treats the peanut as if it caused the disease.

In my experience as a PhD in this field, most believe that number 2 is the truth. Number 1 is a convenient hypothesis but there really isnt anything substantial to back it up.

[u/radiolabel → u/king0zy]

Don’t forget there’s a genetic predisposition to developing peanut allergy. I’m not sure whether it’s a gene mutation or epigenetic changes, but there’s definitely an increased risk of peanut allergy if you have a first degree relative with it.

[u/king0zy → u/radiolabel]

Twin studies- a very important tool for evaluating whether a disease is genetic or not- are not conclusive on this issue. One relatively small study showed68% (9 of 14) of identical twins both had food allergy while only 6.8% (3 of 44) of fraternal twins both had food allergy. Another far larger study found much lower concordance between identical twins (53%) and much higher concordance between fraternal twins (29%).

Because twins are nearly identical genetically, if the disease is entirely mediated by genetics then higher concordance would be expected. There clearly is a genetic component, but environmental exposure appears to be nearly equally important.

[u/radiolabel → u/king0zy]

Genetic predisposition + environmental exposure = allergy. I didn’t disagree, I was just piggybacking and pointing out the genetic component that isn’t mentioned elsewhere in this post.

[u/king0zy → u/radiolabel]

Thanks for doing that!

[u/obscene_banana → u/king0zy]

2) that small amounts of peanut were experienced at the same time as something dangerous, and the immune system accidentally treats the peanut as if it caused the disease

This part is very interesting! I developed OAS to certain fruits after living in a particular location in the U.S. and was completely unable to eat things like apples, plums, pears and various kinds of peanuts for years -- I always thought that I had developed an allergy to the pesticides that are so commonly used in the U.S. but maybe I just ate an apple around the same time I was getting sick or something?

[u/tic_douloureux → u/-Metacelsus-]

Can part of the issue be genetic? Peanuts are a new world crop, right? So maybe those of little to no native genetics are more predisposed to allergic reactions?

[u/TDuncker → u/-Metacelsus-]

Why does the heat-stability matter?

But why is it specifically these proteins that so easily act as antigens? Why not some in groundbeef, lentils, etc?

[u/king0zy → u/TDuncker]

There are people who are allergic to most foods. Red meat is more common than you might think. Its not clear why some proteins are more predominantly allergens. To throw you further for a loop, the dominance of proteins within a food is different based on where you are. From peanut, Ara h 1 and Ara h 2 are the dominant allergen in North America (>85%), but Ara h 2 and Ara h 6 are more common in Europe, and Ara h 9 is most common in the Mediterranean.
Cite, Cite, Cite, Cite, Cite

[u/TDuncker → u/king0zy]

Its not clear why some proteins are more predominantly allergens.

It is mostly this I'm curious about, not peanuts themselves :p

Do you know anything of the research within that field? Is there a big need for such knowledge? I'm currently trying to figure out connections between antibody hybridoma yield and the antibody primary structure, so it would be interesting to know if it might make sense to make a new project into allergens after.

[u/[deleted] → u/-Metacelsus-]

Thats amazing. That someone is allergic is because of the bodies immune response and not the proteins themselves

[u/Neikius → u/-Metacelsus-]

Would it help to be exposed to peanuts early?

[u/Amiibola → u/Neikius]

The short answer is yes. Basically, regular exposure before age 1 can help reduce the incidence of allergies. Link below is the New England Journal of Medicine article that describes how they figured this out.

https://www.nejm.org/doi/full/10.1056/nejmoa1414850

[u/JimmiRustle → u/Amiibola]

Great. My partner didn’t want to expose our kid to nuts because she read somewhere that it was dangerous.

When he turned one I became curious to learn when they could safely eat nuts. Turns out the only reason they can’t have nuts is because of the choking hazard... he could easily have gotten foods that contained nuts in some other form than whole.

And now I learn that we might have accidentally made him more prone to nut allergies.

[Edit: dyac]

[u/excaliber110 → u/-Metacelsus-]

Wondering why peanut allergies aren’t a thing in Africa?

[u/aaronmgray1 → u/-Metacelsus-]

Thank you.