If Your Body Is Making Anti-Gliadin Antibodies, Doesn't That Mean You're Gluten Sensitive?

[Seeking2012]

Ok so I've been thinking about this. If your body is making AGA-IgG or AGA-IgA, doesn't that mean that your body is having an immune reaction to gluten?

AGA-IgG and AGA-IgA are antibodies. Antibodies are products that the body makes in response to what the body thinks is a foreign invader that needs to be killed off. It's an immune response.

If your body is creating ANY sort of immune response to gluten, doesn't that mean you need to stop eating gluten? Long-term low-level immune activity over the long-term could lead to autoimmune diseases or put the body in a state of oxidative stress, right?

What percentage of the population makes AGA-IgG/AGA-IgA antibodies?

[peeptoad]

I've thought about this as well (and also in relation to thyroid disease). I had antibodies present on my celiac blood test, but they were below the level used to diagnose celiac, so I was labeled "non-celiac gluten intolerant" or something like that.

I've also had thryoid anitbodies show up on tests before (and I do have some thyroid-type symptoms), but was told my thyroid was fine because they again below the level used to DX.

[gatita]

I have been wondering this too!!!

I don't understand why the experts say that "some" anti-gliadin antibodies are "normal." Do we produce "some" antibodies for everything we eat?

I'd love to know the answer!

[CaveMum]

According to Open Original Shared Link :

".....look for evidence of gluten harm: this is to make the diagnosis of gluten-sensitivity (reactions to gluten without the gut damage).

• Anti gliadin antibody IgG (Also called IgG-gliadin antibody)
  
• Anti gliadin antibody IgA (Also called IgA-gliadin antibody)
  

A positive test shows that you have an immune reaction to gluten. This might not be causing symptoms yet. Most gluten-sensitive people have a high IgG-gliadin test."

[nvsmom]

My guess is how much we react is the issue. If you compare it to hay fever, some people react really badly and sneeze, swell, get running eyes and noses,hives, and feel horrible when there is pollen in the air, others might just sneeze a few times. Wheat is probably an irritant to many but is only really bad for some... but that is just my guess.

[Seeking2012]

Ok I've thought about this more deeply and now I have all kinds of new questions.

1. Does the fact that the body CAN make an antibody against gluten inherently mean the body is coded to recognize gluten as an antigen (as in, you are born thinking that gliadin is an antigen)? Or does it mean that the body taught itself later on how to make an antibody against gliadin?

2. When the immune system produces antibodies against gliadin, is this a reaction of a "confused" immune system which mistakenly thinks that gliadin is an antigen? Is the immune system wrong about this? What tells the immune system that something is an antigen?

3. The immune system, as we all know, does make mistakes. For example, when it makes killer cells that attack the "self" cells in an autoimmune response, I would consider that to be a confused mistake that the immune system makes. But how did the immune system get confused and think that the "self" cells were antigens or pathogens?

4. How does the immune system make antibodies against a cell it thinks is an antigen or a pathogen? Does this information need to be pre-coded into our DNA, or can the immune system make antibodies against anything and everything that it thinks is an invader? What are the restrictions and limitations on this?

[nvsmom]

I think your questions are great, but I don't think the medical community is close to answering them. they only admitted there was such a thing as autoantibodies about 50 years ago... It does seem that once the body gets confused once, it gets confused again and again. My body has attacked my intestines, thyroid and platelets; I think it would be naive to assume it won't ever attack anything else in me.... something is definitely "off".

Docotrs are investigating a few avenues for causes. I've read about toxins (food and environmental) causing an autoimmune reaction to start. trauma starts it in some, and viruses like EBV are known to kick stat some immune problems. There seems to be a genetic link too.

I doubt they'll figure it out in my lifetime.

[Luddie]

I've come to the same conclusion about the possibility of finding the "answers" in my lifetime. But, I'm still plugging away at eating as gluten-free as I possibly can. My doctor is even more of a stickler on other things, too, like certain foods that are heavy on latex (I'm allergic as are many people apparently), and especially on the balance of Omega 3 and Omega 6s. He has had me on many supplements for the past several years. Yes, I'm sick of taking pills, but I don't have migraines anymore, or cramps in my legs. I've lost about 20 pounds that I needed to lose, and in general my blood tests are coming out pretty well. My major problem is arthritis-like pains, but even they have gotten better using some mild medications (which I'm currently trying to wean myself off of). I'm not "in the pits" like I was for a while (a year or so?!) when I felt absolutely overwhelmed in trying to care for myself when I really didn't feel I knew enough all the while trying to explain to my large family what was happening. Even though loving and caring, they simply didn't know how to help either, except listen and not laugh too much at whatever current "weird" elimination diet I was on! I still get teased and my doctor gets laughed at, too, for "making it up as he goes along." That's okay by me. I want a doctor who is willing to learn from the latest research and change his mind if he feels it right to do so. Anyhow, for those of you just starting on this journey, hang in there. This Forum really helped me during some dark, late computer nights! Thanks to all the dear people who care.

[1desperateladysaved]

I had a blood test which tested for antibodies for 60 or so foods. Of the foods I eat (nearly all tested) I did not have antibodies for 11 of them. The result was I went on a rotational diet, and I am feeling better.

Diana

[plumbago]

Here's my attempt. The numbers are mine, and not meant to refer to the sequence of your questions.

[1]

"When antigens (foreign substances that invade the body) are detected, several types of cells work together to recognize them and respond. These cells trigger the B lymphocytes to produce antibodies, specialized proteins that lock onto specific antigens.

"Once produced, these antibodies continue to exist in a person's body, so that if the same antigen is presented to the immune system again, the antibodies are already there to do their job. So if someone gets sick with a certain disease, like chickenpox, that person typically doesn't get sick from it again.

"This is also how immunizations prevent certain diseases. An immunization introduces the body to an antigen in a way that doesn't make someone sick, but does allow the body to produce antibodies that will then protect the person from future attack by the germ or substance that produces that particular disease.

"Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That's the job of the T cells, which are part of the system that destroys antigens that have been tagged by antibodies or cells that have been infected or somehow changed. (Some T cells are actually called "killer cells.") T cells also are involved in helping signal other cells (like phagocytes) to do their jobs.

"Antibodies also can neutralize toxins (poisonous or damaging substances) produced by different organisms. Lastly, antibodies can activate a group of proteins called complement that are also part of the immune system. Complement assists in killing bacteria, viruses, or infected cells.

"All of these specialized cells and parts of the immune system offer the body protection against disease. This protection is called immunity."

SOURCE: Open Original Shared Link

[2]

"Under certain situations, gliadin (digested gluten) can get to the lamina propria, where it will it will be deamidated (roughly: altered) by tissue transglutaminae (an enzyme). This is a very important step because deamidated gliadine can combine with HLA DQ2 and HLA-DQ8 (genetic markers) on the antigen-presenting cell (macrophages and B cells strategically located in places places antigens are likely to penetrate, including the GI tract) and then will be presented to the T cell, which will secrete cytokines."

From a grand rounds lecture, by Dr Hasan H. Hasan from a couple of years ago, who in turn got much of his information from Fasano (I think). I found it on iTunes U.

[3]

"Patients with Celiac disease create antibodies to gliadin, but these antibodies can also be found in other conditions and in normal people."

Celiac Disease: A Hidden Epidemic (not that much help if you ask me!)

[4]

But how did the immune system get confused and think that the "self" cells were antigens or pathogens?

Picking Dr Hasan back up again (and this is just a slightly educated guess to your question):

" The deamidated gliadin has high affinity for HLA2 and HLA8 (I think he means HLA DQ2, etc), which you have if you have Celiac disease. They are both on the antigen-presenting cell. Will be presented to the T cell. The T cell secretes cytokines which cause pathological changes we see in celiac disease. At the same time, it will also cause stimulation and expansion of B cells and B cells will produce the antibodies which we screen for when we try to diagnose celiac disease."

[U Gluten Free]

The body produces large amounts of IgA antibodies, and these are thought to provide a protective "coating" to the intestine. Antibodies to different foods and microorganisms are common. There is no evidence that the presence of anti-gluten IgA antibodies is important in celiac disease or gluten sensitivity.

[GottaSki]

The body produces large amounts of IgA antibodies, and these are thought to provide a protective "coating" to the intestine. Antibodies to different foods and microorganisms are common. There is no evidence that the presence of anti-gluten IgA antibodies is important in celiac disease or gluten sensitivity.

I am not clear with regard to your statement.

Are you speaking of anti-gliadin antibodies? Both IgA and IgG anti-gliadin antibodies are important measurements in the diagnosis of celiac disease.

Of course the Deamidated Gliadin Peptide tests are preferable to the AGA tests, but this does not make them obsolete.

[mushroom]

The body produces large amounts of IgA antibodies, and these are thought to provide a protective "coating" to the intestine. Antibodies to different foods and microorganisms are common. There is no evidence that the presence of anti-gluten IgA antibodies is important in celiac disease or gluten sensitivity.

The lab ranges for negative, weak positive, and positive, acknowledge that we all produce IgA antibodies. And in fact the total serum IgA measures that we produce sufficient amounts of IgA antibodies for the testing to be valid. It is the number of antibodies that determines whether or not one has celiac disease, not the actual presence of one or more antibodies. Since all the celiac testing done by alleopathic medicine is based on anti-gliadin antibodies, I would like to see your citations for the statements you are making.

[U Gluten Free]

I am not clear with regard to your statement.

Are you speaking of anti-gliadin antibodies? Both IgA and IgG anti-gliadin antibodies are important measurements in the diagnosis of celiac disease.

Of course the Deamidated Gliadin Peptide tests are preferable to the AGA tests, but this does not make them obsolete.

The lab ranges for negative, weak positive, and positive, acknowledge that we all produce IgA antibodies. And in fact the total serum IgA measures that we produce sufficient amounts of IgA antibodies for the testing to be valid. It is the number of antibodies that determines whether or not one has celiac disease, not the actual presence of one or more antibodies. Since all the celiac testing done by alleopathic medicine is based on anti-gliadin antibodies, I would like to see your citations for the statements you are making.

Hi gottaski,

Hi mushroom,

The guidelines for diagnosis have continued to be refined over the years. No doubt, individual physicians will use their discretion regarding what approaches to use in their diagnosis, and antibody tests are just part of the picture. However, as far as i can tell, serology to measure levels of anti-gliadin antibodies is no longer the preferred approach.

I listed couple of the most recent and thorough reviews of this topic below. They are consistent with the informational found on the websites of several clinical research centers.

1. A consensus-building session held in 2012, resulting in the "Oslo Definitions"

The Oslo definitions for coeliac disease and related terms

Gut 2013;62:43–52. doi:10.1136/gutjnl-2011-301346 = Open Original Shared Link

"After introduction in the 1980s, IgA antibodies against wheat gliadin (AGAs) served as the best serological test for celiac disease for some years. However, the low positive predictive value meant that this test has since been abandoned for the investigation of celiac disease, except for in children younger than 18 months, in whom IgA AGA seems to have high sensitivity. Recently, assays for IgA and IgG antibodies against DGP have been introduced and perform similarly to TTG-based tests."

2. World Gastroenterology Organisation Global Guidelines

Celiac disease Open Original Shared Link

[GottaSki]

Hi gottaski,

Hi mushroom,

The guidelines for diagnosis have continued to be refined over the years. No doubt, individual physicians will use their discretion regarding what approaches to use in their diagnosis, and antibody tests are just part of the picture. However, as far as i can tell, serology to measure levels of anti-gliadin antibodies is no longer the preferred approach.

I listed couple of the most recent and thorough reviews of this topic below. They are consistent with the informational found on the websites of several clinical research centers.

1. A consensus-building session held in 2012, resulting in the "Oslo Definitions"

The Oslo definitions for coeliac disease and related terms

Gut 2013;62:43–52. doi:10.1136/gutjnl-2011-301346 = Open Original Shared Link

"After introduction in the 1980s, IgA antibodies against wheat gliadin (AGAs) served as the best serological test for celiac disease for some years. However, the low positive predictive value meant that this test has since been abandoned for the investigation of celiac disease, except for in children younger than 18 months, in whom IgA AGA seems to have high sensitivity. Recently, assays for IgA and IgG antibodies against DGP have been introduced and perform similarly to TTG-based tests."

2. World Gastroenterology Organisation Global Guidelines

Celiac disease Open Original Shared Link

Thank you for clarifying your original statement with regard to "anti-gluten" antibodies.

I concur with these articles - in most cases the DGP should be used rather than the AGA - for those with confusing serology the AGA can be used as part of the work-up.

The key point is that gliadin peptide or protein antibody measurement is an important part of the diagnostic process.

[U Gluten Free]

GottaSki,

I don't claim to be a clinician, and just rely on the published literature and information from celiac disease resource websites. However, it's well known that clinical guidelines are just guidelines. Physicians will use more or less diagnostic resources depending on several factors: particular case, personal preferences, ability to pay for tests. From what I can gather, anti-gliadin serology has poor specificity for celiac disease, and offers little extra value, except in special cases (such as IgA deficiency or diagnosis of infants).

Unfortunately, no test is 100% accurate, and the reliability depends both on the test itself and the particular testing laboratory used. There are several scientific reviews and articles which address the pros and cons of different diagnostic approaches. In general, these reviews are consistent with the two links I posted earlier.

One illustration of current practice would be the University of Chicago celiac disease Research Center, whose website states:

AGA are anti-food protein antibodies; as such, they are not indicative of any autoimmune reactions. They appear only if the patient has been eating gluten, but–and this is the point–they are not linked to any detectable adverse reaction to gluten. In other words, they can appear in individuals who eat gluten as a response to it touching the gut, but do not necessarily correlate with any clinical expressions.

Thus, patients with true non-celiac gluten sensitivity, patients with IBS and no gluten sensitivity, as well as individuals who are totally healthy (perhaps a bit less commonly, but not significantly so) may all have positive (or negative) AGA.

AGA should not be relied upon to prove or disprove the diagnosis of celiac disease or non-celiac gluten sensitivity.

As with everyone else on this forum, I'm here to learn, so please let me know if you have more information.

[mushroom]

Ultimate Gluten Free, I'm glad you clarified that you were talking about the AGA IgA and IgG test only. Certainly I concur that this test is not used much any more since it has been replaced by the DGP (IgA and IgG), a test which some doctors are unfortunately reluctant to run.

[gatita]

"they are not linked to any detectable adverse reaction to gluten."

Arrggh. Feeling very frustrated right now that anti-gliadin IgA, total IgA, and ttg were the only tests my doctor ordered back in July before I went gluten-free.

Why did he bother with this test if it's meaningless?

[mushroom]

The tests run were not all meaningless, gatita. The total IgA is important, and the tTG is commonly used as a 'screening' test in the (IMHO) mistaken belief that this test must be positive for you to have celiac disease. The pp is correct that the DGP has replaced the AGA testing because of its high degree of specificity for celiac disease but it is taking a while for the medical profession to 'relearn' what they 'know' about celiac disease.

[jebby]

"they are not linked to any detectable adverse reaction to gluten."

Arrggh. Feeling very frustrated right now that anti-gliadin IgA, total IgA, and ttg were the only tests my doctor ordered back in July before I went gluten-free.

Why did he bother with this test if it's meaningless?

Hi Gatita,

You may want to check with your lab to see what they mean by anti-gliadin antibodies....my recent labs were done through LabCorp through my M.D.s office and the results which were reported as anti-gliadin antibodies were actually DGP antibodies (as if things weren't confusing enough at baseline). So, perhaps you did actually have the right tests done.

Also, in response to the original post, I have been doing a lot of literature reviews on breastfeeding and gluten and Celiac Disease, and what I learned is that anti-gliadin antibodies are present in the breast milk of all women who consume gluten (even women without celiac disease or non-celiac gluten sensitivity). This supports the notion that very small titers of these antibodies are normal.

[dilettantesteph]

I have seen this thread for awhile, but I didn't actually read it until now. My thinking on this is that if we are producing antibodies, we are reacting. What I think happened is that celiac disease was defined by GI docs by damage to the intestine observed by endoscopy. Sometimes antibodies were observed when GI damage to the intestine was not observed. By their definition, that could not be celiac disease. So, they had to come up with other reasons why the antibodies to gliadin might be elevated. None of those have made sense to me. I think that they don't want to admit that maybe the endoscopy doesn't pick up all damage that might be caused by the auto immune response to gluten. There is DH. There are many with a positive diagnosis for celiac disease because they had a positive test for DH, but a negative endoscopy. The GI docs had to admit that in this case, with DH, it is possible to have a negative endoscopy but still have celiac disease, but in every other case of a negative endoscopy, it isn't celiac disease. Gluten intolerance is a term given to those who experience negative symptoms in response to ingesting gluten, but do not have a positive endoscopy. Whether or not these people create antibodies to gluten is not defined.

I think that the auto immune response damages much more than just the intestine. Just look at all our symptoms, and look at how fast they come on when we get glutened. Surely they can't be just from nutritional deficiencies. I have heard neurologists who are convinced that it is the autoimmune response which is causing the problem. We need more immunologists studying this condition. We need more specialists besides just gastroenterologists looking at this.

[plumbago]

Dr Hasan goes even further by asking - what if the three antibody tests are negative but I still suspect celiac disease?

He says that celiac disease is much more than just a GI disease, citing DH, too, and gluten ataxia, and many other cases. And he notes the nervous system has poor regenerative ability.

He cites the pyramid:

The tip of the iceberg is Active celiac disease - signs and symptoms, check; genetic, check; serology, positive; mucosal damage.

There is Potential - relatives and patients who are at high risk.

And with Latent celiac disease you have normal mucosa, but you have the genetics and presence of antibodies.

Silent celiac disease - with abnormal mucosa and no symptoms.

We need to treat the disease, not the mucosa, he says.

So in the case of suspecting celiac disease in the face of negative testing, Dr Hasan recommends doing a genetic study. If positive, go on a trial of gluten-free diet.

He says 20% of patients w/ DH, have normal mucosa.

Plumbago

[mushroom]

He says that celiac disease is much more than just a GI disease, citing DH, too, and gluten ataxia, and many other cases. And he notes the nervous system has poor regenerative ability.

My own theory is that celiac disease is just one form of gluten intolerance

[Seeking2012]

...anti-gliadin antibodies are present in the breast milk of all women who consume gluten (even women without celiac disease or non-celiac gluten sensitivity).

Are they present in women who have been 100% gluten free for over 2 years?

[Seeking2012]

Here's my attempt. The numbers are mine, and not meant to refer to the sequence of your questions.

[1]

"When antigens (foreign substances that invade the body) are detected, several types of cells work together to recognize them and respond. These cells trigger the B lymphocytes to produce antibodies, specialized proteins that lock onto specific antigens.

"Once produced, these antibodies continue to exist in a person's body, so that if the same antigen is presented to the immune system again, the antibodies are already there to do their job. So if someone gets sick with a certain disease, like chickenpox, that person typically doesn't get sick from it again.

"This is also how immunizations prevent certain diseases. An immunization introduces the body to an antigen in a way that doesn't make someone sick, but does allow the body to produce antibodies that will then protect the person from future attack by the germ or substance that produces that particular disease.

"Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That's the job of the T cells, which are part of the system that destroys antigens that have been tagged by antibodies or cells that have been infected or somehow changed. (Some T cells are actually called "killer cells.") T cells also are involved in helping signal other cells (like phagocytes) to do their jobs.

"Antibodies also can neutralize toxins (poisonous or damaging substances) produced by different organisms. Lastly, antibodies can activate a group of proteins called complement that are also part of the immune system. Complement assists in killing bacteria, viruses, or infected cells.

"All of these specialized cells and parts of the immune system offer the body protection against disease. This protection is called immunity."

SOURCE: Open Original Shared Link

[2]

"Under certain situations, gliadin (digested gluten) can get to the lamina propria, where it will it will be deamidated (roughly: altered) by tissue transglutaminae (an enzyme). This is a very important step because deamidated gliadine can combine with HLA DQ2 and HLA-DQ8 (genetic markers) on the antigen-presenting cell (macrophages and B cells strategically located in places places antigens are likely to penetrate, including the GI tract) and then will be presented to the T cell, which will secrete cytokines."

From a grand rounds lecture, by Dr Hasan H. Hasan from a couple of years ago, who in turn got much of his information from Fasano (I think). I found it on iTunes U.

[3]

"Patients with Celiac disease create antibodies to gliadin, but these antibodies can also be found in other conditions and in normal people."

Celiac Disease: A Hidden Epidemic (not that much help if you ask me!)

[4]

But how did the immune system get confused and think that the "self" cells were antigens or pathogens?

Picking Dr Hasan back up again (and this is just a slightly educated guess to your question):

" The deamidated gliadin has high affinity for HLA2 and HLA8 (I think he means HLA DQ2, etc), which you have if you have Celiac disease. They are both on the antigen-presenting cell. Will be presented to the T cell. The T cell secretes cytokines which cause pathological changes we see in celiac disease. At the same time, it will also cause stimulation and expansion of B cells and B cells will produce the antibodies which we screen for when we try to diagnose celiac disease."

All of that does help me understand the subject better (I hope). What it sounds like to me, in very basic language, is this:

1. The presense of gliadin causes the intestine's epithelial cells to overproduce zonulin (why does this happen?)

2. Zonulin is a protein that causes the tight junctions between epithelial cells to open up.

3. Due to this opening, gliadin particles are allowed to reach the lamina propria, which is known to be an area that produces lots of antibodies.

4. While in the lamina propria, the body attempts to break down gliadin further because it is a long chain protein molecule that cannot be used by the body in its original amidated state. The enzyme tissue transglutamase deamidates (breaks down partly) the gliadin protein.

5. In people with the HLA-DQ2 and/or HLA-DQ8 halotype, their cells will recognize the deamidated (broken-down gliadin) protein as an antigen, and begin producing antibodies against it. Perhaps this is because those people who evolved the HLA-DQ2 and/or HLA-DQ8 halotype long ago were selected for some other reason (and the antibodies they make against self tissue were meant to attack a different antigen that looks like the self tissue) that has nothing to do with gliadin; perhaps it gave them an advantage in their original environment. Perhaps someone can clue me in as to the reason that the HLA-DQ2/DQ8 halotype would have been naturally selected and in what environment it would have been selected.

6. For some unknown/unclear (to me) reason, the body will then also produce antibodies against the enzyme that helped break down gliadin protein (tissue transglutaminase). Perhaps someone else can figure this part out.

All of this is just about convincing me to go into the field of biology; it is quite fascinating to me.

Dr. Alessia Fassano seems to believe that one of the solutions to fix this problem is a medication that suppresses the release of zonulin. Although this would allow people to eat gluten-containing foods without a reaction, it would also create a dangerous situation in which the body would not be able to send viruses and bacteria down to the lamina propria for destruction (unless I'm presenting this too simplistically).

Any comments/corrections/thoughts on this?