Is There An Expert In Immunology Here?

[poopedout]

I decided to put this in as a new topic as I am afraid it is going to get lost where it was and I would like to know if anyone here knows the answer to my question.

I need this response to small amounts of gluten to make sense scientifically. I have been doing some research to see if I can understand why just a little bit of gluten could cause such a huge reaction after going gluten free when I was eating much larger amounts of gluten before. From what I have read it has to do with the immune response. The cells that produce the antibodies to gliadin have a memory from when I was eating more gluten and now when just a small amount of the antigen, gliadin, is introduced there is a very fast and vigorous response to the antigen. In other words the pump has been primed. If that is correct why would it take two months of eating gluten again to produce the antibodies and have a positive test? Does anyone know the answer to that?

[ravenwoodglass]

There is a big difference between the amount of antibodies that are produced and their action on our systems and the amount of antibodies need to show up in blood work. Some of us even under full long standing autoimmune attack will have false negative blood tests. Hopefully someone will be able to explain it a bit more fully but even the experts don't really know why some of us can be so sick and still show up negative on blood work unless new research has shed some light on this.

[Skylark]

It takes one or two months for the mucosal celiac immune response to be so widespread and severe that the celiac antibodies move from the intestinal mucosa to the bloodstream (if they ever do). There is research where folks with celiac biopsy and negative or only anti-gliadin IgA serology show deposits of celiac antibodies in the mucosa. As you know, in people with celiac the local inflammatory response in the mucosa from eating gluten never goes away.

I don't know why people seem to get more sensitive. I don't know whether we feel better, so the response seems more severe or whether there is a separate immunological mechanism at work. I haven't seen any research.

[Jestgar]

I have heard of the immune system down-regulating itself in response to constant exposure (but I have no links for you). This would mean that after years of being exposed to gluten, your entire immune response is muted (both to gluten and other diseases). Once you remove gluten, your immune system recovers and responds to the occasional intrusion of the nasty demon the way it has wanted to all along, but was too tired to do.

[Jestgar]

Some of us even under full long standing autoimmune attack will have false negative blood tests. Hopefully someone will be able to explain it a bit more fully but even the experts don't really know why some of us can be so sick and still show up negative on blood work unless new research has shed some light on this.

RWG, this is my take on this.

Until recently, the only recognized body response to gluten was in the intestine. All the tests were designed specifically to recognize what gluten is doing to the intestine.

It's not at all unreasonable to think that the antibodies to gluten that cause problems in other parts of the body are sufficiently different (recognize a different conformation/modification of gluten) that these antibodies are not detectable in the tests that currently exist.

You can only find what you are looking for.....

[Skylark]

And looking in the blood is probably the wrong place much of the time. Things like DH and gluten ataxia are very localized. Blood is just relatively easy to sample, so diagnostic tests tend to rely on it.

[Jestgar]

And looking in the blood is probably the wrong place much of the time. Things like DH and gluten ataxia are very localized. Blood is just relatively easy to sample, so diagnostic tests tend to rely on it.

Looking under the streetlamp for your keys, even though you lost them in the bushes.

[ravenwoodglass]

RWG, this is my take on this.

Until recently, the only recognized body response to gluten was in the intestine. All the tests were designed specifically to recognize what gluten is doing to the intestine.

It's not at all unreasonable to think that the antibodies to gluten that cause problems in other parts of the body are sufficiently different (recognize a different conformation/modification of gluten) that these antibodies are not detectable in the tests that currently exist.

You can only find what you are looking for.....

That makes a great deal of sense. I do wish this country would adopt the mucosal testing methods where a gluten suppository is used either rectally or orally and then the antibodies are looked for in the mucosal cells after a couple of hours. From my understanding we don't use the test here because it is a very sensitive test and picks up antibodies in folks that don't have gut destruction. In other words the test can be positive for the antibodies but not enough folks have villi destruction so it is considered too sensitive or to produce false positive results. When oh when is this country going to recognize that celiac is not just a gut disease!

[nora-n]

The reason one gets such huge responses to just traces of gluten after going gluten-free is freshly activated T cells.

They are researching this response now several places to try to make a new celiac test. One must be gluten-free for at least a week to get this freahly activated T cell response.

I tried to enroll in such a study.

[Marz]

Thanks for asking this question, I'm keen to hear about these mechanisms as well. Just to throw in my 2 cents, though I'm no expert - the immune system is incredibly powerful.

Think how quickly and violently an allergic person can react to peanuts, bee stings, shellfish?

Sometimes even the smell of something can set off the reaction due to micro-particles hanging around in the air (I'm thinking of true wheat allergy here, I think flour can set people off?)

Now imagine that reaction occuring specifically in your intestine, or in other parts of your body. Swelling, increased blood flow to the area, T-cells attacking the actual cells. And then that damage is stimulating the GIT to cramp up, move the offending food away as quickly as possible. The damage still hangs around for days afterwards, because it takes a while for the swelling to go down, the intestine to repair itself etc.

With it being constantly bombarded with the offending item, firstly all the immune cells involved are constantly being used up and stimulated. Imagine a "shortage" of the required components required for the extensive chain reaction that is your immune system. Now without the offending gluten, your body has stored up all the components and cells it needs, it's like a warehouse of immune reaction waiting to be unleashed upon your intestine. The trigger is small, but the chain reaction can become huge.

Is it correct to say, that if small amounts of gluten causes an extreme reaction in your body, that you are definately setting off an immune reaction and should then by definition avoid gluten like the plague, as the gluten-antibody complexes can cause extensive damage anywhere in your body?

[poopedout]

The reason one gets such huge responses to just traces of gluten after going gluten-free is freshly activated T cells.

They are researching this response now several places to try to make a new celiac test. One must be gluten-free for at least a week to get this freahly activated T cell response.

I tried to enroll in such a study.

So the freshly activated T cells are in the gut and it takes two months of eating gluten again for the antibodies to show up in the blood and cause a positive tTg test?

[nora-n]

no theya re in the blood and one ahs toe at gluten for three days, then draw blood and they find the freshly activated T cells in the blood.

Does not work if one is still eating gluten.

[poopedout]

no theya re in the blood and one ahs toe at gluten for three days, then draw blood and they find the freshly activated T cells in the blood.

Does not work if one is still eating gluten.

Are these killer T cells or helper T cells?

Do these T cells produce the antibodies that eventually show up in the blood?

I still don't understand why one can get so sick soon after eating a small amount of gluten and why it takes two months of eating gluten again to get enough antibodies for a positive blood test.

[poopedout]

I have been doing some more research and I think I found an answer to one of my questions. It is very interesting. In this paper it says that going gluten free removes the antigen that stimulates T-cell mediated tissue damage in the gut, but it does not remove the immune response and may heighten the immune response stimulated by gluten since regulatory T cells are typically not maintained unless antigen exposure continues. They say this may explain why gluten exposure triggers more dramatic symptoms following adoption of a gluten-free diet than during chronic gluten exposure associated with untreated celiac disease.

Now I have to find out more about these regulatory T cells.

[poopedout]

It looks like the regulatory T cells are suppressor T cells and they suppress autoimmune responses. Also the suppressor activity of the regulatory T cells is significantly impaired in celiac patients.

[Marz]

Thanks for the clear explanation. The immune down regulation also explains why cheating on a gluten free diet can be worse for your health than being blissfully unaware. Google for "celiac mortality in relatives" - there was an unexpected increase in death rate to partial adherance to diet compared to undiagnosed/total non compliance. At least that's what I interpreted the short abstract as. Would love to see the results on this study

[poopedout]

Are these killer T cells or helper T cells?

Do these T cells produce the antibodies that eventually show up in the blood?

I still don't understand why one can get so sick soon after eating a small amount of gluten and why it takes two months of eating gluten again to get enough antibodies for a positive blood test.

I think I have figured out the answer to the second part of this question. The two reactions are quite different. The reaction after eating a small amount of gluten is an immune response with a lack of suppression and the antibody test is based on the tissue damage in the gut and it seems to take a long time for the antibodies to build up enough to be measured in the blood.

[Tina B]

And looking in the blood is probably the wrong place much of the time. Things like DH and gluten ataxia are very localized. Blood is just relatively easy to sample, so diagnostic tests tend to rely on it.

The gastroenterologist who diagnosed me in 1990 said that a duodenal biopsy is the only difinitive diagnosis. Anitgliadin antibodies were positive but siad it should be confirmed by biopsy. Result was "severe celiac disease". Just don't go gluten free before having a biopsy.

[sb2178]

The gastroenterologist who diagnosed me in 1990 said that a duodenal biopsy is the only difinitive diagnosis. Anitgliadin antibodies were positive but siad it should be confirmed by biopsy. Result was "severe celiac disease". Just don't go gluten free before having a biopsy.

In 1990, that was! The blood tests have improved even since I was first tested about 10 years ago, so the combo can be close to definitive if there are no conflicting results (4/5: genes, diet response, + bloodworks, symptoms, positive biopsy). Still not perfect though... and not enough work looking at the development of the disease. It's sad that your intestines have to be pretty badly damaged to be caught as an official celiac via biopsy.

[ravenwoodglass]

It's sad that your intestines have to be pretty badly damaged to be caught as an official celiac via biopsy.

And tragic for those who have other systems like the brain impacted severely first or those whose intestinal damage is beyond the reach of the scope.

[Zizzle]

I'm reading this thread with great interest. I had positive Enterolab testing done and have been 99% gluten free for a month. I see my internist in one week and will ask for a Celiac panel then. If I start eating gluten now, is that enough time to get an accurate result in one week?

I dread eating gluten again. A couple of mix-ups this month (corn chips and corn tacos made with gluten at Moe

[ravenwoodglass]

I'm reading this thread with great interest. I had positive Enterolab testing done and have been 99% gluten free for a month. I see my internist in one week and will ask for a Celiac panel then. If I start eating gluten now, is that enough time to get an accurate result in one week?

I dread eating gluten again. A couple of mix-ups this month (corn chips and corn tacos made with gluten at Moe

[Zizzle]

A week is not enough time for a challenge for diagnosis purposes. You would need to be back on gluten for a couple months. It sounds like your body has already given you the answer though.

So let's say I skip the bloodwork and go straight to a biopsy. Do the same rules apply? Or do my microscopic colitis and chronic diarrhea suggest I might show villi damage without having to consume tons of gluten for weeks before the test? Again, I've only been gluten free 30 days - that's not enought time to heal the villi, no?

[Skylark]

So let's say I skip the bloodwork and go straight to a biopsy. Do the same rules apply? Or do my microscopic colitis and chronic diarrhea suggest I might show villi damage without having to consume tons of gluten for weeks before the test? Again, I've only been gluten free 30 days - that's not enought time to heal the villi, no?

Hold on. You didn't mention the microscopic colitis before. With a positive Enterolab result and a response to a gluten-free diet, I believe you actually have a very strong diagnosis of gluten sensitive microscopic colitis.

I'm not a fan of Enterolab because his tests are overly sensitive and have low specificity. (I finally found where Dr. Fine talks about the way he has tuned the tests that way deliberately in his own lectures.) Thing is, he is a longstanding expert on microscopic colitis. The history of his fecal antibody testing was to identify gluten sensitivity in people with microscopic colitis who did not recover. The autoimmune disease is in the colon, not the small intestine, so the celiac biopsy can be looking in the wrong place. Without heavy villous damage the celiac bloodwork isn't positive, even though the colitis responds really well to a gluten-free diet.

You will find this an interesting read.

Open Original Shared Link

[nora-n]

A month glutenfree will maybe, or most likely, obscure the results but the lab needs to know you have been gluten free for a month, that way they can look for more subtle changes.