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Why Is The Endomysial Antibody So Specific To Celiac?

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I have noticed throughout my research and speaking to doctors that the endomysial antibody is "a thin connective tissue layer that covers individual muscle fibers. Anti-Endomysial antibodies are developed in reaction to the ongoing damage to the intestinal lining." -http://labtestsonline.org/understanding/analytes/celiac-disease/tab/sample

Ok, so it is created in damage to the small intestinal villi and there are several causes of such damage, here are some of the many:

Coeliac Disease

Cows Milk Protein Intolerance

Soy Protein Intolerance

refractory Sprue

collagenous Sprue

Immunodefiency Synodromes

Mediterranean lymphoma

intestinal ulceration

Gastroenteritis

Intractable Diarrhoea of Infancy

Protein Calorie Malnutrition

Kwashiorkor

Tropical Sprue

Parasitic Disease:

Giardiasis

Strongyloidiasis

Coccidiosis

Intestinal Capillariasis

Hookworm Disease

Eosinophilic Gastroenteritis

Contaminated bowel Syndrome

Drug and Radiation Damage

Understanding this, why would the endomysial antibody have a 95 percent specificity? Some even say it is closer to 100 but it seems most of the causes of intestinal damage can be much more common than celiacs. In my opinion if TTG and EMA only assess damage than there should be a high reliability on other antibody's that are specific to gluten reactions to make sure it is not coming from something else. Should the DGP not be the one that is close to 100 percent specific?

Another scary thing- EMA is elevated in intestinal lymphoma, that is why I feel it is so necessary to have a biopsy.

What do you guys think?

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I have noticed throughout my research and speaking to doctors that the endomysial antibody is "a thin connective tissue layer that covers individual muscle fibers. Anti-Endomysial antibodies are developed in reaction to the ongoing damage to the intestinal lining." -http://labtestsonline.org/understanding/analytes/celiac-disease/tab/sample

Ok, so it is created in damage to the small intestinal villi and there are several causes of such damage, here are some of the many:

Coeliac Disease

Cows Milk Protein Intolerance

Soy Protein Intolerance

refractory Sprue

collagenous Sprue

Immunodefiency Synodromes

Mediterranean lymphoma

intestinal ulceration

Gastroenteritis

Intractable Diarrhoea of Infancy

Protein Calorie Malnutrition

Kwashiorkor

Tropical Sprue

Parasitic Disease:

Giardiasis

Strongyloidiasis

Coccidiosis

Intestinal Capillariasis

Hookworm Disease

Eosinophilic Gastroenteritis

Contaminated bowel Syndrome

Drug and Radiation Damage

Understanding this, why would the endomysial antibody have a 95 percent specificity? Some even say it is closer to 100 but it seems most of the causes of intestinal damage can be much more common than celiacs. In my opinion if TTG and EMA only assess damage than there should be a high reliability on other antibody's that are specific to gluten reactions to make sure it is not coming from something else. Should the DGP not be the one that is close to 100 percent specific?

Another scary thing- EMA is elevated in intestinal lymphoma, that is why I feel it is so necessary to have a biopsy.

What do you guys think?

This is a very good question and I am sorry that I can't answer it! We have some lab experienced people here so maybe they can chime in.

My other comment was that to try and not be so afraid of cancer. Many elevated lab tests and symptoms are caused by a number of things, as you can see, and cancer usually is low on the list of causes. The vast majority of Celiacs heal fine and do not go on to develop lymphoma so declining a biopsy is not that critical for most people.

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...Understanding this, why would the endomysial antibody have a 95 percent specificity?

...

I haven't gotten as far as I expected, but was curious enough to start looking into this.

Isn't part of it because the antibodies are in a category of autoimmune antibodies, so that they don't show in ALL cases of tissue damage, but only in those where damage was caused by the AI antibodies?

Then instead of being an effect or symptom of damage, if they're there they're part of the cause? Would that be true?

(Am I gonna get ripped for thinking out loud? Hope not)

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I haven't gotten as far as I expected, but was curious enough to start looking into this.

Isn't part of it because the antibodies are in a category of autoimmune antibodies, so that they don't show in ALL cases of tissue damage, but only in those where damage was caused by the AI antibodies?

Then instead of being an effect or symptom of damage, if they're there they're part of the cause? Would that be true?

(Am I gonna get ripped for thinking out loud? Hope not)

No, endomysial and TTG both are markers of inflammation. Will they be elevated in every single case of the mentioned causes of villi damage? No, but for some people they will, everyone has different reactions to things, the same strain of salmonella can barely harm one person and kill the next.

I thought the same thing as you but have spoken to many surgeons who are used to signs of inflammation and what to look for, all have claimed that some antibodies are also used as signs of inflammation and damage. That being said, there are several different antibodies that are the direct cause of damage, endomysial and ttg are not one of them.

I guess the reason why endomysial is considered so specific for celiac is because they did the study groups on healthy people with no recent infections/trauma. Perhaps they should change their claims to 99 percent specific in healthy populations.

I suppose it is similar to the ANA, it can be positive in someone with a recent infection as well.

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I thought the same thing as you but have spoken to many surgeons who are used to signs of inflammation and what to look for, all have claimed that some antibodies are also used as signs of inflammation and damage. That being said, there are several different antibodies that are the direct cause of damage, endomysial and ttg are not one of them.

I too was curious after you posed your question, have been doing a bit of reading and had a similar thought to Tom's - do you know which antibodies can be the direct cause of tissue damage? Perhaps a better question would be -- do you have a reference for endomysial antibodies not causing tissue damage? I'll give it another search myself as well.

Thanks!

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I too was curious after you posed your question, have been doing a bit of reading and had a similar thought to Tom's - do you know which antibodies can be the direct cause of tissue damage? Perhaps a better question would be -- do you have a reference for endomysial antibodies not causing tissue damage? I'll give it another search myself as well.

Thanks!

The endomysial is a sign of ongoing intestinal damage, they will be released from the muscle layering of your endomysium when chronic villous atrophy occurs. What will happen is you receive damage in the small intestine for whatever reason, EMA ab's are then released, and yes they cause further damage to the tissue but their release was not from a reaction to gluten but from ongoing inflammation in the small intestine which is what celiacs is. So in the case of a transient attack due to lets say gastroenteritis, the damage occurs, the antibodies are then released in a small transient titre, they do their damage for a while and then they die off. This is known as "post viral transient autoimmunity". As to what antibody starts the attack for celiacs I am not sure yet, will ask next time I go in.

It is important to remember that not everyone with other issues will receive EMA titres because you have had to have a considerable amount of damage for them to be released, E coli would be a good example of patients that would receive transient titres of EMA.

Unfortunately the only link I have was that lab tests online and there are a few studies on NCBI about "transient autoimmune reactions to viral and bacterial infections". If you read through some of those tests you will see that many people who had some sort of infectious illness will have transient ANA, rhematoid, thyroglobulin, ttg elevations depending on the area of affect from the illness.

For example here is one on TTG involvement in non intestinal infectious illnesses- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810390/

You will notice for that test they took mostly kids who had non gastrointestinal illnesses and many had transient TTG elevations. Now the point of the EMA is that it is ONLY involved in the small intestine so if you did not have an illness affecting that area you will not have an elevated EMA, unless you have celiac.

My doctors stressed the importance of titres when looking into the reaction. They said for EMA you would typically be less than 1:10 with TTG under 40 to consider transient autoimmunity and other causes of villi damage. Of course if someone goes in with a TTG over 100 and an EMA of 1:50 they will probably have celiacs but that is why it is such an individual basis.

I will get some articles together and post them up soon. I find the problem with internet research is they always put everything into a one size fits all mentality, which absolutely CANNOT be used in the medical world.

One other thing, specificity is created by population samples, they take healthy patients that have had no infections or illnesses in the past year and among these patients the ones that had positive EMA were more likely to have celiacs than other more rare non infectious causes I.e- intestinal lymphoma. That is why the specificity is 95-99 percent in those cases, those poor poor people who had intestinal lymphoma... However articles I have read and will need to pull up shot down EMA to as low as 80 percent specificity in certain instances.

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I've. read much of the same info, but remain very interested in all causes of intestinal damage/villous atrophy.

Thanks :)

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I've. read much of the same info, but remain very interested in all causes of intestinal damage/villous atrophy.

Thanks :)

Pulled up something interesting on biopsies and villi damage:

"Small intestinal biopsy does however, have some limitations. For example, acute viral gastroenteritis and allergy to cow's milk or soy protein can cause abnormal small intestinal biopsies that are indistinguishable from celiac disease. However, acute viral gastroenteritis is not easily confused with celiac disease because of the difference in the acuteness of symptoms. (Acute viral gastroenteritis has a sudden onset of symptoms and last only a few days.) It is however, easier to confuse cow's milk and soy protein allergies with celiac disease, but these allergic conditions are rare and primarily occur in young children. Despite these limitations, small intestinal biopsies are recommended even for individuals who have abnormal antibody tests for celiac disease."

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/celiac-disease-malabsorptive-disorders/

"Pathologic changes on small-bowel biopsy are characterized by a spectrum of abnormalities described by Marsh and known as the Marsh criteria (Box 2). The hallmark of celiac disease is Marsh 3 or villous atrophy; however, this may be patchy or present in other disorders as in hypogammaglobulinemia, acute infectious gastroenteritis, or milk intolerance. Additionally, there is growing evidence that celiac disease may be diagnosed when changes of earlier phase on biopsy such as Marsh 1 or Marsh 2 are seen" http://americanceliac.org/celiac-disease/diagnosis/

Going by this, if gastroenteritis and cow's milk intolerance can cause similar damage to celiac then it would bring up the same markers of damage (EMA, and TTG). That is why I think it is so important to look at more than just one antibody to test for damages and to stress the importance of the DGP test to verify the cause of damage in the intestine.

I guess we have me as the little test dummy to figure out if these theories are correct, should be retesting my blood sometime in December.

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And another article on similarities in other gastro issues and celiac

http://surgpathcriteria.stanford.edu/gi/celiac-disease/differential-diagnosis.html#t1

After reading all that I have I would HATE to be a gastroenteroligist, the entire digestive system just seems like a mess and diseases from it are very difficult to diagnose with really no slam dunk diagnosis most of the time.

Funny how things like thyroid, liver etc.. can all be diagnosed with one simple blood test.

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Yep...I can certainly attest to the frustration of the patient doctors are unable to diagnose in cases of non-responsive celiac and other autoimmune disorders.

There is much more to learn with regard to the human digestive system.

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Pulled up another good article on some of the tests and what they mean:

http://drrodneyford.com/faq/bloods-tests/gluten-blood-tests.html

"Celiac disease is defined as the gut damage caused by gluten. When this happens, there is an over-reaction of the immune system in the gut. A harmful immune reaction is generated in the gut tissue. This tissue injury involves inflammatory cells and the production of antibodies. These “tissue damage” tests are very accurate and can detect this damage."

tTG antibody (also called IgA tissue transglutaminase antibody)

The tTG antibody test is a tissue damage test. tTG is a specific antibody made against muscle tissue damage in your small bowel. It is a very sensitive indicator of the small bowel damage that can be caused by the gluten in your diet. High levels of tTG mean that you might have gut damage (celiac disease). It is currently recommended that you confirm the likelihood of gut damage by having a small bowel biopsy (by endoscopy).

Value of tTG: If very high, then celiac disease almost certain. If slightly high, then maybe celiac. Not so reliable in young children.

Notice the bold here... The TTG detects small bowel damage that CAN be caused by gluten. Key word CAN, not ONLY.

"EMA (Endomesial Antibodies)

This is an older test and becoming less popular. Nevertheless, it is quite sensitive at detecting the gut tissue damage of celiac disease.

Value of EMA: If positivie, then high chance of celiac disease."

"This is a newer type of gliadin test, initially developed and manufactured by Inova Diagnostics. It was developed to more accurately identify people with celiac disease. Eventually, it might overtake the tTG test because it is excellent at finding those people who have gluten gut damage. This test detects an immune response to a very specific fragment of the gluten molecule (this fragment is a short peptide of gliadin – a gliadin peptide). Although this test is excellent for detecting celiac disease (in our Clinic I have found it to be more reliable that the tTG test), it does not detect gluten sensitivity.

Value of DGP: If both high, then celiac disease is almost certain. Perhaps more reliable than tTG for young children."

There you have it, EMA and TTG are inflammatory reactions to small intestinal tissue damage, most often celiacs but NOT ALWAYS. Very important to catch the reason of the damage, verification with DGP and a gluten free diet is paramount in obtaining the right diagnosis.

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Dug up some more info on specificity tests and how infections can raise antibodies. These are different than the endomysial but share the same specificity for their respective diseases.

anti-Saccharomyces cerevisiae antibodies (ASCA)- This is considered the endomysial of Crohn's disease, with a 98.9 percent specificity to the disease.

Now here is a study in which these antibodies were elevated amongst others in nonautoimmune patients during acute infection:

http://www.ncbi.nlm.nih.gov/pubmed/17894023

So if an antibody with a almost 99 percent specificity to Crohn's can be elevated during infections there is no reason to assume different with the endomysial although I am having trouble finding studies on it being done on patients with infectious disease. Maybe it is so outdated that doctors stopped caring? That is almost the feel I have gotten during my research.

Will keep this page updated with info as I learn. Hopefully this will help others understand antibody circulations in different population samples.

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Does anyone have anything to add? A lot of people on the forum seem to think EMA has a strong correlation to celiacs in all population samples, can you guys comment or add some literature to support that? I am very curious as to why it is praised to such high specificity when I have seen nothing validating what it is either than "a reaction to ongoing inflammation in the small intestine".

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A lot of people on the forum seem to think EMA has a strong correlation to celiacs in all population samples...

I don't think it's that a lot of us think it's a high correlation in all population samples. I feel you could be over generalizing here...

As far as I can remember, EMA is 90-95% specific to celiac (but i haven't researched it for a while since I am satisfied with my diagnosis). So I think that means that 90-95% of people with a positive EMA have celiac. That just means that 5-10% of people with a positive test have something else wrong with them like an infection. There aren't many illnesses that cause your body to continue to attack your intestines after it's under gone some previous damage like celiac does. The thing is, as I see it, is that many who suspect celiac realize if they've have an infection like e.coli and know the sudden onset of symptoms could be caused by that. It's when the symptoms continue much longer than they should that celiac is suspected because celiac is often started by some sort of trigger, just like many other health problems are.

I personally tested positive for ttg IgA (I think it was >200 with a range of 0-20) and EMA (1:40). With those two tests showing damage has happened, or was happening, with my lifelong history of stomach issues and other autoimmune disease cropping up, and then with my positive response to the gluten-free diet, I am sure it was celiac. And if it wasn't celiac, then whatever it was seems to have gone into remission. I'm sure I was one of the 90-95% here.

I think in 90-95% of positive EMA cases, if it looks like a duck and quacks like a duck, it probably is a duck. Celiac is expressed with "a reaction to ongoing inflammation in the small intestine" so when people test positive for it, it's probably celiac.

Best wishes. I hope you get your situation figured out.

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I don't think it's that a lot of us think it's a high correlation in all population samples. I feel you could be over generalizing here...

As far as I can remember, EMA is 90-95% specific to celiac (but i haven't researched it for a while since I am satisfied with my diagnosis). So I think that means that 90-95% of people with a positive EMA have celiac. That just means that 5-10% of people with a positive test have something else wrong with them like an infection. There aren't many illnesses that cause your body to continue to attack your intestines after it's under gone some previous damage like celiac does. The thing is, as I see it, is that many who suspect celiac realize if they've have an infection like e.coli and know the sudden onset of symptoms could be caused by that. It's when the symptoms continue much longer than they should that celiac is suspected because celiac is often started by some sort of trigger, just like many other health problems are.

I personally tested positive for ttg IgA (I think it was >200 with a range of 0-20) and EMA (1:40). With those two tests showing damage has happened, or was happening, with my lifelong history of stomach issues and other autoimmune disease cropping up, and then with my positive response to the gluten-free diet, I am sure it was celiac. And if it wasn't celiac, then whatever it was seems to have gone into remission. I'm sure I was one of the 90-95% here.

I think in 90-95% of positive EMA cases, if it looks like a duck and quacks like a duck, it probably is a duck. Celiac is expressed with "a reaction to ongoing inflammation in the small intestine" so when people test positive for it, it's probably celiac.

Best wishes. I hope you get your situation figured out.

Great response, I am sorry if I sounded like I was over generalizing, it is just that I have seen many people (not all) say 100 percent specific, if it is positive you have it no doubt. I was looking for those people to chime in as to where they got their info from.

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I've seen it said that with more than one positive test, a patient could be considered 100% specific but I have not idea where I read that.

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Just ran into a new study that showed the endomysial providing an astonishing 64 percent specificity in their screening population.

http://www.crd.york....&ID=21998000181

http://www.ncbi.nlm.nih.gov/pubmed/9459047

Effectiveness results

EMAs had a sensitivity of 95% and specificity of 64%. The only predictor of positive biopsy that reached statistical significance was a positive EMA.

Clinical conclusions

Diagnosis of celiac disease presents a difficult problem for clinicians. Because the patients are frequently children, clinicians and parents are often reluctant to perform small bowel biopsy, a relatively invasive procedure, to make the diagnosis. Serological tests are more acceptable; EMA in particular has high sensitivity and specificity in select populations at risk of having celiac disease.

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