Comment by hirenj | Hacker News Reader

Comment by hirenj | Hacker News Reader

Guess what? It's glycotime again!

Gal(ɑ1,3)Gal (Galili epitope) is a common epitope in most animals, but in primates we lost the activity of the gene (GGTA1) to synthesise it. Since we don't produce it any more, it's recognised as foreign by our body and not only causes rejection in xenotransplantation, but also this Alpha-Gal allergy.

I'm not going to comment on the actual immune mechanisms that take place with developing an allergy to a carbohydrate epitope, beyond saying that I don't understand enough of it. Somehow we lose the tolerance to this antigen that we develop from about 6 months of life.

I'm more interested in what makes this epitope: Is this carbohydrate synthesised by the actual ticks, or is it actually something to do with a tick-associated parasite or the microbiome? Here's a review (https://pubmed.ncbi.nlm.nih.gov/31214181/) that covers this that I quickly found, suggesting that (a member of) the microbiome can in fact alter levels of ɑ-Gal from ticks.

edit: Obviously, the solution to this problem would be to just eat primate meat instead, which is one hell of a risky bet given our problematic pandemic primed populations.

Also fascinated by the fact that it's possible to lose tolerance to something you've ostensibly recognized as "okay" for most of your life, but I mostly wanted to just say that "problematic pandemic primed populations" got a hearty chuckle out of me.

Well, allergies are almost always "something you tolerated most of your life (until then)" ... in my understanding you're not born with immune-intolerance to something (although you are most certainly born with a disposition or lack thereof), and not always is the manifestation of an allergy your system's first encounter with that specific protein - it is simply chance.

E.g. the possibly most prevalent allergies, against pollen, manifest well after kindergarten, or even in teenagers. Until then the system did not care at all about pollen. The reason must be something entirely unrelated to pollen. And there are more and more cases of people developing pollen allergies well after age 50! (But: often you will find other allergies or "pre-symptoms" in kids, e.g. neurodermatitis or milk-protein allergies).

In fact you always develop the allergy on exposure AFAIK - it just might be the first exposure. But the reason is most often completely unrelated to this specific substance/protein.

There are even several known substances that are known to cause allergies to develop on exposure (with high probability). But what you become allergic to is pure chance, e.g. could be the nickel-plated jewelry on your skin which you never had a problem with until then.

All food allergies can work like this, as do with other immune malfunctions like celiac disease. Having the allergies/autoimmune sensitivity from birth is not as common as developing them later on. It can happen at any time in life! Most people tolerate the allergen for some period of time, and then their immune system’s response changes for reasons unknown.

I have allergies to shellfish and tree nuts (plus celiac disease - gluten) diagnosed/developed later in life, along with oral allergy syndrome which sometimes causes a painful reaction to a wide range of foods, but only sometimes (depends on immune state). While I’ve never had an anaphylactic reaction, my allergist prescribed an EpiPen, saying the reactions often increase in severity suddenly with no warning.

> Obviously, the solution to this problem would be to just eat primate meat instead

What if we gene-edited our babies to have GGTA1 again from birth?

Short answer is we probably don’t know what will happen.

Long answer: We probably lost the enzyme activity during a fight with some pathogen. The truncated protein is still produced, and there are effects in the body if that is removed. So, putting it back (under the same expression programming) might do nothing bad, or it might break all the other hacks we’ve accumulated since we first lost the enzyme, or it might not protect against this allergy, or we might be more susceptible to some bacterial beastie that we should really mount immune responses to. Don’t think anyone has tried activating it again in any animal/model system.

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