Hypothetical question about antibodies

[Zuma888]

Good day,

From browsing this forum, I've come to find out that even on a gluten-free diet, many people seem to take years for their antibodies to go down to normal levels, and also that hidden gluten could keep the levels from going down to normal indefinitely. Shouldn't that mean that a celiac person would have a high possibility of testing positive given that they had gone gluten free for less than 2 years or so, and especially if they had not been careful about cross-contamination or had cheat days? The criteria for the gluten challenge makes it seems like the possibility of false negative is high in general.

[Scott Adams]

That’s a really insightful observation about antibody testing and the gluten challenge! You’re absolutely right that antibody levels can remain elevated for months or even years after going gluten-free, especially if there’s ongoing cross-contamination or occasional slip-ups. The immune system doesn’t reset overnight—it can take time for antibodies like tTG-IgA to normalize, which is why many doctors recommend waiting at least 6–12 months of strict gluten-free eating before retesting. For someone who’s been gluten-free for less than two years or hasn’t been meticulous about avoiding cross-contact, there’s absolutely a chance they’d still test positive, since even small amounts of gluten can keep antibodies elevated. This is partly why the gluten challenge (where you eat gluten before testing) exists—it’s designed to provoke a measurable immune response in people who’ve been gluten-free long enough for antibodies to drop. But you raise a great point: the challenge isn’t perfect, and false negatives can happen if the timing or amount of gluten isn’t sufficient to trigger a strong antibody response. This is why diagnosis often combines antibody tests with other tools like genetic testing or endoscopy. Your question highlights just how nuanced celiac testing can be!

For people with celiac disease hidden gluten in their diets is the main cause of elevated Tissue Transglutaminase IgA Antibodies (tTG-IgA), but there are other conditions, including cow's milk/casein intolerance, that can also cause this, and here is an article about the other possible causes:

 

 

 

[Zuma888]

Thank you Scott for your helpful response!

Based on this, would you say someone who is on a gluten-free diet - but not strict about cross-contamination and occasional cheating - and tests negative for tTg-IgA while having normal total IgA is not likely to have celiac, even if they have been 'gluten-free' for years?

[Zuma888]

I just got my test results after a less than 2-week gluten challenge consuming about 5 g of gluten per day on average. 

Anti tTG-IgA: <0.2 AU/ml (<8 is negative)

IgA: 180 mg/dl (Reference range is 70-400)

I previously had been on a gluten-free diet for around 3 years or so, with occasional cheating and not being strict about cross-contamination. I am however still suffering from the effects of the gluten challenge (food sensitivities, slight brain fog, weird stool, fatigue, swollen thyroid, bodyaches). Is this likely to be NCGS rather than celiac disease given the test results and my history?

Note: I have one copy of HLA-DQ8.

[Scott Adams]

15 hours ago, Zuma888 said:

Thank you Scott for your helpful response!

Based on this, would you say someone who is on a gluten-free diet - but not strict about cross-contamination and occasional cheating - and tests negative for tTg-IgA while having normal total IgA is not likely to have celiac, even if they have been 'gluten-free' for years?

No, I would not say this at all. If you were diagnosed with celiac disease and were gluten-free for a while, you could have gone into remission. Everyone's body is different, and some celiacs may be able to get regular contamination and not end up with damaged villi and positive antibody tests, while others who ingest tiny amounts will relapse and have full blown symptoms and flattened villi. 

Only a full gluten challenge would reveal where you are at this point. Here is more info about how to do a gluten challenge for a celiac disease blood panel, or for an endoscopy:

Quote

"...in order to properly diagnose celiac disease based on serology and duodenal histology, doctors need patients to be on gluten-containing diets, even if they are causing symptoms, and this is called a "gluten challenge."

• Eat gluten prior to celiac disease blood tests: The amount and length of time can vary, but is somewhere between 2 slices of wheat bread daily for 6-8 weeks and 1/2 slice of wheat bread or 1 wheat cracker for 12 weeks 12 weeks;
• Eat gluten prior to the endoscopic biopsy procedure: 2 slices of wheat bread daily for at least 2 weeks;

and this recent study recommends 4-6 slices of wheat bread per day:

 

 

[knitty kitty]

@Zuma888,

The antibodies produced in response to gluten are made in the intestines.  When the body is provoked sufficiently, the antibodies overflow out of the intestines and into the blood stream.  Once in the blood stream, the antibodies can be measured with tTg IgA tests. 

Three grams of gluten per day for two weeks minimum is enough gluten to make you feel the symptoms of having been glutened, but the antibodies are not in sufficient quantity to be measured in the blood.

Ten grams of gluten per day for a minimum of two weeks is required to get the anti gluten antibodies at a high enough level in the blood stream to be measured by tTg IgA tests.

So, no, occasional cross contamination or (heaven forbid) intentional cheat days will not be sufficient for tTg IgA testing.  You will still be making antibodies which will still be causing inflammation and damage to the intestines and body.  Histamine is released as part of the immune response to gluten.  High histamine levels lead to food sensitivities, brain fog, and body aches.  

The damage done to the gastrointestinal tract affects the absorption of essential vitamins and minerals.  Malabsorption of fats can cause changes in stools.  Insufficient absorption of vitamins and minerals can cause damage to other organs like the thyroid if it can't get enough Selenium, iodine, iron, zinc, and Thiamine.  Brain fog and fatigue can be caused by low Thiamine and other B Complex vitamins.  Vitamin D is needed to regulate the immune system. 

One gene is all that's needed to develop Celiac disease.  I know a Celiac diagnosis is a change that can be difficult to get your head around.  Many people go through the five stages of grief.  One stage is "bargaining".  Sounds like you're stuck there.  Every little cheat counts to your detriment.  But sticking to a gluten free diet, makes every meal a success.  

Read the comments below the article...

Best wishes!  Keep us posted on your progress!

[Zuma888]

6 hours ago, knitty kitty said:

@Zuma888,

The antibodies produced in response to gluten are made in the intestines.  When the body is provoked sufficiently, the antibodies overflow out of the intestines and into the blood stream.  Once in the blood stream, the antibodies can be measured with tTg IgA tests. 

Three grams of gluten per day for two weeks minimum is enough gluten to make you feel the symptoms of having been glutened, but the antibodies are not in sufficient quantity to be measured in the blood.

Ten grams of gluten per day for a minimum of two weeks is required to get the anti gluten antibodies at a high enough level in the blood stream to be measured by tTg IgA tests.

So, no, occasional cross contamination or (heaven forbid) intentional cheat days will not be sufficient for tTg IgA testing.  You will still be making antibodies which will still be causing inflammation and damage to the intestines and body.  Histamine is released as part of the immune response to gluten.  High histamine levels lead to food sensitivities, brain fog, and body aches.  

The damage done to the gastrointestinal tract affects the absorption of essential vitamins and minerals.  Malabsorption of fats can cause changes in stools.  Insufficient absorption of vitamins and minerals can cause damage to other organs like the thyroid if it can't get enough Selenium, iodine, iron, zinc, and Thiamine.  Brain fog and fatigue can be caused by low Thiamine and other B Complex vitamins.  Vitamin D is needed to regulate the immune system. 

One gene is all that's needed to develop Celiac disease.  I know a Celiac diagnosis is a change that can be difficult to get your head around.  Many people go through the five stages of grief.  One stage is "bargaining".  Sounds like you're stuck there.  Every little cheat counts to your detriment.  But sticking to a gluten free diet, makes every meal a success.  

Read the comments below the article...

Best wishes!  Keep us posted on your progress!

Thank you very much @knitty kitty!

I'm glad you brought up the point about histamine. I have been taking an antihistamine after meals where I don't feel so good and never knew why it helped so much. At first I thought I might have a food allergy, but I recently did a food allergy test and I actually have ZERO food allergies.

Regarding your last point about the stages of grief, are you saying it's likely that I have celiac? I have Hashimoto's BTW and I know for sure that gluten causes an autoimmune response to my thyroid as my anti-TPO and anti-Tg go up and my throat feels swollen. Could the symptoms be due to that autoimmune response?

[Zuma888]

14 hours ago, Scott Adams said:

No, I would not say this at all. If you were diagnosed with celiac disease and were gluten-free for a while, you could have gone into remission. Everyone's body is different, and some celiacs may be able to get regular contamination and not end up with damaged villi and positive antibody tests, while others who ingest tiny amounts will relapse and have full blown symptoms and flattened villi. 

Only a full gluten challenge would reveal where you are at this point. Here is more info about how to do a gluten challenge for a celiac disease blood panel, or for an endoscopy:

and this recent study recommends 4-6 slices of wheat bread per day:

 

 

Thanks @Scott Adams! I guess my question now is: do the celiacs who can get away with regular contamination without villi damage as you mentioned have to be strict about cross-contamination ? 

[knitty kitty]

59 minutes ago, Zuma888 said:

Regarding your last point about the stages of grief, are you saying it's likely that I have celiac? I have Hashimoto's BTW and I know for sure that gluten causes an autoimmune response to my thyroid as my anti-TPO and anti-Tg go up and my throat feels swollen. Could the symptoms be due to that autoimmune response?

You have one gene for Celiac.  You have a second autoimmune disease, Hashimoto's thyroiditis, which is frequently found at a higher rate with Celiac.  HLA genes carry autoimmune disease genes like Celiac and Hashimoto's and diabetes and others.  

You have Celiac symptoms of reacting after gluten.  You said "I am however still suffering from the effects of the gluten challenge (food sensitivities, slight brain fog, weird stool, fatigue, swollen thyroid, bodyaches)."  And your anti-thyroid antibodies increase after gluten exposure.  While tTg IgA does not directly attack the thyroid, gluten exposure does trigger the  immune system to produce antibodies against the thyroid in genetically predisposed individuals. 

You did not eat sufficient gluten (10 grams of gluten per day for two weeks minimum) to raise the autoimmune antibodies to the point they can be measured in the blood, so your blood tests may well be inaccurate. 

You could choose to continue the gluten challenge of 10 grams a day for at least two weeks and get retested.  

At the very least, you know that gluten is harmful to your thyroid, and because you are genetically predisposed to Celiac disease, a strict gluten free diet would be beneficial for your overall health.  

[Zuma888]

29 minutes ago, knitty kitty said:

You have one gene for Celiac.  You have a second autoimmune disease, Hashimoto's thyroiditis, which is frequently found at a higher rate with Celiac.  HLA genes carry autoimmune disease genes like Celiac and Hashimoto's and diabetes and others.  

You have Celiac symptoms of reacting after gluten.  You said "I am however still suffering from the effects of the gluten challenge (food sensitivities, slight brain fog, weird stool, fatigue, swollen thyroid, bodyaches)."  And your anti-thyroid antibodies increase after gluten exposure.  While tTg IgA does not directly attack the thyroid, gluten exposure does trigger the  immune system to produce antibodies against the thyroid in genetically predisposed individuals. 

You did not eat sufficient gluten (10 grams of gluten per day for two weeks minimum) to raise the autoimmune antibodies to the point they can be measured in the blood, so your blood tests may well be inaccurate. 

You could choose to continue the gluten challenge of 10 grams a day for at least two weeks and get retested.  

At the very least, you know that gluten is harmful to your thyroid, and because you are genetically predisposed to Celiac disease, a strict gluten free diet would be beneficial for your overall health.  

Thank you so much.

[Scott Adams]

7 hours ago, Zuma888 said:

Thanks @Scott Adams! I guess my question now is: do the celiacs who can get away with regular contamination without villi damage as you mentioned have to be strict about cross-contamination ? 

Great question! Even if some individuals with celiac disease don’t experience immediate villi damage from occasional cross-contamination, it’s still strongly recommended to maintain strict avoidance of gluten. The immune response triggered by gluten can vary between individuals, and even small amounts may cause systemic inflammation or other symptoms, even if intestinal damage isn’t immediately detectable. Additionally, repeated exposure—even at low levels—could lead to cumulative harm over time. Strict avoidance of cross-contamination remains the safest approach to prevent long-term complications and ensure overall health. Everyone’s sensitivity differs, so working with a healthcare provider to tailor precautions is ideal.