Does more gluten = higher ttg?

[deanna1ynne]

For someone who has celiac disease, does higher gluten intake equate to a higher ttg? Or is there likely some ceiling to how high your ttg goes that's perhaps more dependent on your body and your own immune reaction? I know that ttg is supposed to return to "normal" with enough time on a strict gluten-free diet (except for refractory celiac), but is the reverse true? That the more gluten you take in, the higher it will push your ttg? Or will it flat-line at some point, even if you ate nothing but gluten all day, every day (and basically killed yourself... lol)?

[RMJ]

I haven’t read of any scientists doing this experiment with gluten in celiac patients (probably unethical) so I can only make an educated guess based on general immunology knowledge and my experience being responsible for antibody production in rabbits (for use in medical diagnostic tests).

For a while, introducing more of an antigen will make the antibody titer to that antigen increase.  However, what I saw in rabbits, was that this did not go on indefinitely.  It leveled off and eventually decreased some.

Something else interesting was that the antibody titers were extremely variable between rabbits, with the same dose of antigen, even though laboratory rabbits are highly inbred (genetically similar).

[deanna1ynne]

2 minutes ago, RMJ said:

I haven’t read of any scientists doing this experiment with gluten in celiac patients (probably unethical) so I can only make an educated guess based on general immunology knowledge and my experience being responsible for antibody production in rabbits (for use in medical diagnostic tests).

For a while, introducing more of an antigen will make the antibody titer to that antigen increase.  However, what I saw in rabbits, was that this did not go on indefinitely.  It leveled off and eventually decreased some.

Something else interesting was that the antibody titers were extremely variable between rabbits, with the same dose of antigen, even though laboratory rabbits are highly inbred (genetically similar).

That's really interesting! Thank you so much for sharing!

[deanna1ynne]

23 hours ago, RMJ said:

For a while, introducing more of an antigen will make the antibody titer to that antigen increase.  However, what I saw in rabbits, was that this did not go on indefinitely.  It leveled off and eventually decreased some.

Ok, I realize we’re totally in the realm of educated guesses here (so no disclaimer needed!! 😂) , but I’ve been thinking about this more and wondered if you have any estimates of how long the antibody titer would increase? Is that also highly dependent on the subject? 
 

I know I’ve read that 6-8 weeks may not be long enough for a gluten challenge in adults (according to some research that suggests that it may take longer for the ttg levels to rise significantly.) Is there any kind of estimate, like your numbers will go up for 3-6 months, and then likely stabilize or even go down?

[RMJ]

Most of the studies in the literature are usually trying to see how short a gluten challenge can be, so they don’t look for what you’re interested in.

Here is a paper that does look at 2 weeks vs 4 weeks of gluten challenge and it certainly hasn’t leveled off by 4 weeks (see figure 2).  The figure only shows the average results.  The ranges listed in the text are quite wide - i.e. much variation between individuals.

Gluten Challenge Kinetics

Here is a literature review.  Section 3.3 specifically discusses antibodies in children. They mainly say what percentage of children became antibody positive after different lengths of challenges, not how positive they were.  They did note that for the older anti-gliadin tests in some studies the percentage who were positive went up then eventually decreased over time.

Clinical Response to Gluten Challenge

So educated guess, if you could get your doctor to test at 3 months, and if not 10X normal test again at 6 months, you’d probably have the best chance of getting the official diagnosis via antibody level.

[deanna1ynne]

Thank you!! I am super excited to read all of this!

[deanna1ynne]

On 12/4/2021 at 2:52 PM, RMJ said:

So educated guess, if you could get your doctor to test at 3 months, and if not 10X normal test again at 6 months, you’d probably have the best chance of getting the official diagnosis via antibody level.

Well, I'm not sure what happened, but we upped her gluten intake significantly (gave her a biscuit made from straight up vital wheat gluten - no actual flour - estimated to have 20g of gluten each, based on how many we made and how many servings of gluten/protein was in the package) for 4 weeks, and then gave her two biscuits a day for the last two weeks (i.e., around 40g of gluten daily) and tested again, and her ttg-iga levels actually went down from 6X the upper level in November to only 3X the upper level yesterday. It seems really counter-intuitive and I don't know how to understand it. Her deamidated gliadin igg also moved from the "strong positive" to the "weak positive" range (24 with a cut-off of 20). 

Can your body just get used to gluten? I have no idea how to interpret this, when I was so sure before that she had celiac disease (ttg iga was 6X the upper limit with a positive EMA). If more gluten means less ttg-iga, does it mean we just had it wrong before when we thought she had celiac disease, you think?

[knitty kitty]

4 hours ago, deanna1ynne said:

Well, I'm not sure what happened, but we upped her gluten intake significantly (gave her a biscuit made from straight up vital wheat gluten - no actual flour - estimated to have 20g of gluten each, based on how many we made and how many servings of gluten/protein was in the package) for 4 weeks, and then gave her two biscuits a day for the last two weeks (i.e., around 40g of gluten daily) and tested again, and her ttg-iga levels actually went down from 6X the upper level in November to only 3X the upper level yesterday. It seems really counter-intuitive and I don't know how to understand it. Her deamidated gliadin igg also moved from the "strong positive" to the "weak positive" range (24 with a cut-off of 20). 

Can your body just get used to gluten? I have no idea how to interpret this, when I was so sure before that she had celiac disease (ttg iga was 6X the upper limit with a positive EMA). If more gluten means less ttg-iga, does it mean we just had it wrong before when we thought she had celiac disease, you think?

"Predicting vital wheat gluten quality using the gluten aggregation test and the microscale extension test"

https://pubmed.ncbi.nlm.nih.gov/33367286/

Looks like there's some variety in vital wheat gluten.  

Perhaps regular wheat flour would be more provocative of a reaction and higher ttg readings.  

 

[Onegiantcrunchie]

Isn't it a measure of the body's immune response to the gluten, not the amount of gluten solely?

So, if your body is a certain amount reactive to gluten, the more you eat of it, the higher the antibody level would be. But if you're not that reactive, then that same amount of gluten would give you a lower level of antibodies. And if you're not coeliac you can live and breathe biscuits and never get gluten antibodies.

When I had a positive TTG on a gluten-free diet, I was told by the doctor doing the endoscopy that either I'm still eating trace amounts of gluten, or I have an "aggressive form of the disease".

Hope this helps.

[knitty kitty]

I found an article that explains well how gluten causes inflammation....

Attack of the Gluten

https://www.acs.org/content/acs/en/education/resources/highschool/chemmatters/past-issues/archive-2011-2012/gluten.html

 

And an article on the difference in wheat flour and gluten content...

https://healthyeating.sfgate.com/gluten-content-flours-11162.html

Hope this helps!