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< The antigen will always destroy your cells, autoimmune response or not.

In regards to autoimmunity, antigens themselves don't destroy cells--antigens only provoke a pathogenic immune response when presented to the immune system.

< Celiac is typically an autoimmune response to Gliadin protein as a result of human leukocyte activation genes HLA-DQ2.2/2.5 or HLA-DQ8. In either case, it is happening at the cellular level for every cell that comes into contact with the protein.

You're not wrong with regards to the celiac, gliadin, and the association with the HLA alleles that you've mentioned. However, I'll point out that those particular HLA genes make up MHC class II proteins. These are the proteins present on what are known as professional antigen presenting cells, a small group of specialized immune cells throughout the body. MHCII proteins present foreign antigen to TH4 cells (helper T cells) which can then activate a larger immune response.

Epithelial cells of the intestinal villi have not classically been thought to be professional antigen presenting cells, and thus should have very small levels of expression. I found one older study (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC508181/) that suggests these intestinal villi cells can express class II but nothing since. All of this suggests that the pathogenesis of celiac disease is not as simple as intestinal villi cells expressing high levels of the HLA proteins encoded by the genes you mentioned and provoking a direct immune response--rather, like seemingly every autoimmune disease, the story is much more complicated and likely involves the activation of CD4+ T cells, generation of pathogenic autoantibodies, and a larger network of pro-inflammatory players.

> The immune response is therefore not entirely autoimmune in nature but necessary to protect the cells. The vili are being destroyed directly, essentially.

Isn't the damage to villi a byproduct of the (auto)immune reaction? I haven't studied it in depth, but what I've read seems to indicate that the damage is caused by inflammatory reactions (as part of the immune response) rather than directly from the prolamins.

> The antigen will always destroy your cells, autoimmune response or not. Sensitivity depends on how many (one or two) of the HLA genes you have that react with gluten.

The gluten is not reacting with genes, but the genes help determine how your immune system responds to the antigen, so it's still entirely an immune response, at least as I understand it.

Thanks for this- it sounds like I need to do some more research to completely understand whats going on, but this is very helpful. If you dont mind my asking, are your symptoms mostly GI related? Ive heard others can have symptoms that manifest in things like sinuses getting plugged up or skin rashes. Also sounds like a drug similar to Humara may be something that could provide at least some relief to the immune response.

No. Mine were mostly cognitive. I mean, when I was a kid I had no tooth enamel (had to have surgery to install fake teeth) and puked up everything I ate that had wheat in it, but somehow no one diagnosed it until later. I just assumed it was normal but my symptoms were migraines, anxiety, stomach bloating, joint pain, hair loss, stunted growth, constant fatigue, sleep apnea, nutrient deficiencies, malabsorption. It took about a year to feel better. It used to be cross contamination would mean 3 days of pain, gluten 7 days. Now cross contamination is a worthy trade off for occasional meal out, and gluten is 2-3 days in small amounts. I shudder to consider eating a full bun or something but I haven't tried in years. I know within 10 minutes because the skin inside my mouth peels off. So I kind of have systems for managing it. I have a normal job and would say it has not really hindered me outside of eating a very strict diet. Having support from my partner also helps a great deal. It's good you caught it early.

"I shudder to consider eating a full bun or something but I haven't tried in years."

I have it nowhere near as bad as you (which is why it went undiagnosed until I was 30... although it's still pretty bad). But for about 5 years after I found out I would have recurring dreams where I would be eating a hamburger and realize after swallowing "Oh, crap, that's a normal bun!" I suppose in some sense that might qualify as a nightmare the first couple of times, because it would fully wake me up.

I also have Celiac disease, somewhat less severe than nibstwo, and I also have recurring dreams where I eat something (usually pizza) and midway through realize it is made with wheat dough. This was further compounded when once I ate a package of vegetarian chicken wings (made of wheat gluten) which was mislabeled at the grocery store (gluten free tag on the price label) and next to veggie burgers by the same brand with the same packaging where ARE gluten free and I had eaten before without a problem... I was sick for about a week, couldn't work or think straight. I won't make that mistake twice!

Another funny angle--I also have Type 1 diabetes (diagnosed when I was 9) and for a long time after diagnosis I had dreams about drinking a 64oz soda only to realize it wasn't diet, and panicking since I would probably be in DKA soon after!

Maybe there is some immune system disease/nightmare link that has gone undiscovered :)

Thanks for sharing. Those symptoms sound quite horrific. My daughter had some similar symptoms as well. She had 4 cavities when she was 3. I think she was too young at the time to articulate how she felt but I know she also had some cognitive difficulties(and is only now just getting caught up to grade level despite being a VERY EARLY talker and having a large vocabulary for a toddler)