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Hompes MethodPractitioner Training Level II

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Lesson Ten

“Gluten Sensitivity Testing”

Gluten - Introduction

• Gluten sensitivity and coeliac disease provide plenty of talking points over and above the previous lesson’s content. Gluten is a major problem and is covered initially in Hompes Method Level I. In this lesson I want to cover coeliac and gluten sensitivity testing in detail.

Why Test?

• No matter how unpleasant symptoms might be, the only way to convince some folk to avoid gluten is to show them a piece of paper that tells them they have a problem with gluten. I’ve worked with people where this was the case even when they feel 100% better when they avoided the gluten!

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Why Test?

• The gluten iceberg shows us that many people are walking round with symptoms that may seem to be completely unrelated to something like gluten. Furthermore, gluten can cause “silent” problems where people are blissfully unaware of the damage being caused each time they eat gluten.

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Why Test?

• The iceberg analogy is a great way to explain the problems of gluten sensitivity and coeliac disease.

Why Test?

• Gluten sensitivity and coeliac disease can cause serious complications and increase the risk of death from all causes if gluten consumption continues. Gluten appears to be involved in the aetiology of at least 55 diseases!

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Why Test?

• One study looked at almost 30,000 patients from 1969 to 2008 (39 years) and examined deaths in three different groups:

1. Those with confirmed celiac disease

2. Intestinal inflammation from gluten

3. Latent Coeliac Disease (genetically predisposed)

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Why Test?

• Here’s what they found:

– 39% increased risk of death from all causes in those with confirmed celiac disease.

– 72% increased risk of death from all causes in those with gut inflammation related to gluten.

– 35% increased risk in the genetically predisposed folk.

(Ludvigsson JF, Montgomery SM, Ekbom A, Brandt L, Granath F. Small-intestinal histopathology and mortality risk in celiac disease. JAMA. 2009 Sep 16;302(11):1171-8.)

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Why Test?

“With few exceptions, research has shown an increased risk of death in celiac disease.”

JAMA, Sept 16, 2009, Vol 302, No.11.

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Why Test?

“Cardiovascular disease was the most common cause of death in coeliac disease, followed by malignancy.”

JAMA Sept 16, 2009, Vol 302. No.11

“Excess mortality was observed independent of histopathology.”

JAMA Sept 16, 2009, Vol 302. No.11

• In other words, the amount of damage done to the intestine did not correlate with mortality rates.

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Why Test?

“Individuals with coeliac disease are treated with a gluten free diet, while very few with (gluten-induced) inflammation are. Those with inflammation may have

an overall worse prognosis than those with villous atrophy, since institution of a gluten-free diet often

leads to normalization of the mucosa.”

JAMA Sept 16, 2009, Vol 302. No.11.

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Why Test?

They found a greater increase in risk of death in people who were gluten-sensitive but who were NOT coeliac. This is a profound finding because western medicine really only considers coeliac disease. It ignores other segments of the gluten sensitivity spectrum (iceberg).

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Remember the Iceberg

• People with gluten sensitivity who are tested and come back negative for coeliac disease will tend to continue eating gluten. They believe the test result and they their doctor’s words (medical dogma).

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Why Patients and Docs Don’t Test

1. Classic symptoms are so common and perceived to be part of “normal life”.

2. Non-classic symptoms aren’t linked back to problems in the gut (energy, aches, sleep, skin, etc.)

3. Silent symptoms are, well, silent!

– Thus, patients don’t bother to ask for testing and, in their minds, docs have no reason to test.

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Your Dad Didn’t Have It…

“Currently, screening for coeliac disease is not routinely carried out in England. It is usually only recommended

for people at an increased risk of developing the condition, such as those with a family history of the

disease. It is recommended that first-degree relatives (parents, brothers, sisters and children) of people with

coeliac disease are screened.”www.NHS.co.uk

* What about gluten sensitivity, and what about the fact that your family may not have been tested (or had a false negative result)?

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Diagnostic Delay

“The majority of celiac patients had visited 5 or more doctors prior to diagnosis…and it had taken an average

of 5 to 10 years, after initial presentation (of symptoms), for Celiac Disease to be diagnosed.”

American Celiac Society, Nov 9, 1996.

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Diagnostic Delay

“Death was most significantly affected by diagnostic delay, pattern of presentation and adherence to a gluten-free diet…non-adherence to the gluten-free-diet, defined as eating gluten once per month increased the relative risk of death 6-fold. Our results emphasize the need for prompt diagnosis and treatment also in those patients with a minor or symptomless form of celiac disease.”

Lancet Vol. 358, August 4, 2001.

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Summary So Far…

• Clearly the literature points to a need for prompt diagnosis, but there’s a major problem with getting the diagnosis made. And don’t forget, we’re only talking about coeliac disease here, not the full gluten sensitivity spectrum.

It’s Not An Easy Diagnosis

• It is not that easy to diagnose coeliac disease and harder still to diagnose gluten sensitivity. It’s not clear cut and the testing methods are fraught with difficulty and inaccuracy. This is one of the reasons patients find themselves wandering from doctor to doctor trying to figure out why they have symptoms.

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Standard Coeliac Tests

• A test called Tissue TransGlutaminase antibody (tTG) is the primary test ordered to screen for celiac disease):

– It’s a blood test that requires a full blood draw.

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Standard Coeliac Tests

• The Endomysial Antibody (EMA) test is less frequently used:

– Another blood test that requires a full blood draw.

tTG and EMA?

• The Endomysium is like “cling-film” around muscle fibres.

• Tissue transglutaminse is a collection of enzymes within the endomysium.

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tTG and EMA Inaccuracy

• tTG and EMA tests are extremely accurate when total villous atrophy is present. This is where the shags in the intestinal carpet have been completely worn down. But they lose accuracy in the earlier stages of the disease where the intestines are just inflamed or only partially damaged.

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“Antibody positivity correlates with more severe villous

atrophy, and not mode of presentation.”

“Seronegative Coeliac disease occurs.”

Dig Dis Sci, Vol 49. No.4, (April 2004), 546-550

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“Recent data showed that serology (not only EMA but also anti-tTG) seems to be ineffective in detecting most of the patients affected by subclinical/silent disease.”

Digestive and Liver Disease 39, 2007, 30-32.

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“One study evaluating EMA, for example, showed that the sensitivity of this marker was 100% in patients with total villous atrophy. But the value plummeted to 31% accuracy in patients with who only had partial villous

atrophy.”

New Eng J Med, Oct 23, 2003, 1673-4.

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Inaccuracies in tTG and EMA Tests

“Patients with classical disease and total villous atrophy were endomysial antibody positive 77% of the time,

whereas those with classical disease and partial villous atrophy were endomysial positive only 24% of the

time.”

Dig Dis Sci. Vol 49, No.4. 546-550.

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Inaccuracies in tTG and EMA Tests

“Patients with non-villous atrophy gluten sensitivity (Marsh I, Marsh II) are more likely to test negative for

tTGA and EMA.”

Proceedings of the Nutrition Society, 2009, 68, 234-241.

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• The previous slide is taken from a presentation on the Mayo Clinic website.

• Mayo clinic has the reputation as being the best in North America in many areas, including diagnostics. They don’t mention the info I’ve shared with you in their online presentation on coeliac disease.

• I think that’s scary.

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• The medical literature points to the fact that early diagnosis is key, yet the standard tests are inaccurate unless patients have already developed total villous atrophy. So we have a complete paradox here! Let’s continue dissecting the medical tests and showing why they must be interpreted with care and caution.

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“The use of one serological marker is insufficient for establishing the true prevalence of celiac disease.”

Am J Gastro. Vol 97, No.10, 2002

“Both EMA and tTG should be performed; a significant proportion of patients will be missed if only one of

these tests is performed.”Dig Dis Sci. Vol 49, No.4. 546-550

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• In many settings, only tTG will be performed Thus, we have yet another stumbling block in the diagnostic procedure.

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Coeliac Testing Procedures

• Gluten has to be eaten frequently for 1-2 months before the tTG and EMA tests are performed. Failure to do this may provide a false-negative result. Of course, this can cause major problems for people who’ve been on a GF-diet and are already healing.

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Other Celiac Markers

• The gluten molecule has sub-components, one of which is a molecule called gliadin. A test can be added to the coeliac testing panel to identify something called a deaminated anti-gliadin antibody.

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Other Celiac Markers

• Sometimes a total immunoglobulin-A (IgA) test is ordered. IgA molecules are like the front line immune defense in the mucosal barrier – nostrils, intestine, vaginal tract, eyes, etc. IgA “soldiers” can be depleted in gluten sensitive and celiac patients. Over the years I’ve seen a lot of people with “burned out” IgA levels and I always suspect gluten issues in these people.

.

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Other Coeliac Markers

“Celiac disease patients are 10-15 times more likely to

exhibit IgA deficiency.”

Alt Med Rev, Vol 10, Number 3, 2005.

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Other Coeliac Markers

• A biopsy of the small intestine may be examined to detect damage to the intestinal villi to confirm celiac disease, However, given the invasive nature and cost of a biopsy, tTG and EmA antibody tests are often used to identify those individuals with high probability of having celiac disease.

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Confusion!

• This can all be very confusing – imagine feeling better when you avoid gluten only to be told your coeliac blood tests are “negative” or “normal”. This happens to a lot of people. To reiterate, it’s really important to note that standard tests are only relevant in coeliac disease and not the whole gluten sensitivity spectrum. Yet it’s the people with early/mid progression inflammation who are, perhaps most at risk.

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Confusion!

“Individuals with celiac disease are treated with a gluten free diet, while very few with (gluten-induced) inflammation are. Those with inflammation may have

an overall worse prognosis than those with villous atrophy, since institution of a gluten-free diet often

leads to normalization of the mucosa.”

JAMA Sept 16, 2009, Vol 302. No.11.

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Dissecting Gluten

• Gluten is not a single substance; rather it is a mish-mash of different molecules, including sub types of gluteninand gliadin. Different people can react to different sub types.

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Dissecting Gluten

“We found that 50% of these patients do not respond to the alpha-GLIA peptide but to a diverse set of gliadin

and glutenin peptides…Although some patients respond to one set of peptides, others respond to different sets

of peptides…Our present results indicate that CD patients are capable of responding to a large array of

gluten peptides.”

Gastroenterology 2002;122:1729-1737.

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Dissecting Gluten

“An analysis of the gluten proteome has led to the identification of as many as 60 putative peptides that

have similar characteristics.”J. Dent Res 87(12):1100-1107, 2008.

“Interestingly, truncated peptides 17-mer, 18-mer, and 13-mer were as potent as 33-mer in eliciting T-cell

responses.”J. Immunol 2009;182;4158-4166.

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Private Labs

• Private labs understand the problem in more detail and have some great tests, not just for celiac disease, but also for gluten sensitivity in general. As you’ve seen already, the latter is obviously missing in the medical system.

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Genova Coeliac Panel

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Cyrex Laboratory – Array 1

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Cyrex Laboratory

“In patients with active celiac disease, IgA antibodies to disease-precipitating gliadin are reliably represented in

whole saliva.”

Ann. N. Y. Acad. Sci. 1098: 288-311 (2007)

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Cyrex Laboratory

“Measurement of salivary IgA AGA provided excellent discrimination between those children with coeliac

disease and the control groups, and our study suggests that it may provide a rapid, non-invasive method of

screening for this disease before intestinal biopsy.”

Arch of Dis in Childhood: 1992; 67: 724-727.

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Cyrex Laboratory

“Our salivary test proved to be sensitive and specific, having a good correlation with the relative serum

samples… In fact 31 of 32 children positive with saliva were confirmed by serum test, and 28 of 29 children

who underwent intestinal biopsy showed villous

atrophy.”

– JPGN 2011; 52: 17-20

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Cyrex Laboratory Array 2


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Anti-Gliadin sIgA (stool or saliva)

• This test is a nice starting point: it doesn’t provide direct information on celiac disease but when an anti-gliadin IgA is high, or very low, I suspect a problem with gluten and generally insist on further testing. Elevations in the anti-gliadin IgA suggest a person’s immune system is reacting to dietary gluten. I’ve learned that even moderate elevations in anti-gliadin IgA levels can indicate severe problems with gluten.

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Anti-Gliadin sIgA - Case Study

• You can see elevated anti-gliadin sIgA in this example from a 27-year old professional soccer player. When he eliminated gluten, the transformation in his energy levels, sleep and mood were truly profound. It’s interesting to note that he had no obvious digestive symptoms, despite considerable levels of inflammation in his gut.

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Gluten Free Diet as a “Test”

• Many people still believe a gluten free diet to be the best diagnostic tool. I both agree and disagree with this idea. Sure, a 30-60 day gluten free trial is a great way to determine whether gluten is causing problems, as long as the patient is experiencing obvious symptoms. But it can’t differentiate between coeliac disease and gluten intolerance and nor is it of any help in “silent” cases.

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Gluten Free Diet as a “Test”

• “Classic” symptoms can improve very quickly indeed on a GFD. Non-classic symptoms may take longer to improve. If gluten is not avoided for long enough, patients may not feel improvements. Remember: silent GS and CD will not be identified.

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When to Use Lab Testing

• Lab work is definitely helpful for many people, as long as financial resources can cater for the testing. If folk can’t afford lab testing, I simply recommend a strict gluten-free diet! The key point is to ethically advise patients/clients of gluten’s dangers so they may make their own decisions.

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Gluten Sensitivity Testing - Summary

• Testing is more complex than most doctors really understand.

• Classic coeliac testing – tTG and Ema – are only accurate when villous atrophy has already developed.

• Using one of these tests without the other also decreases accuracy.

Gluten Testing Summary

• Total IgA as well as anti-gliadin markers can be addedto augment the testing.

• A gluten free diet is a great test in its own right, but it’s no good in cases where “silent” problems are occurring.

• Both Genova Diagnostics and especially CyrexLaboratory carry very good coeliac and gluten testing.

Thank You!

• As always, thanks so much for consuming this information. I hope you found the lesson interesting and helpful. Gluten is a major issue and it’s important you consume the information in the lesson resource section.

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