Gluten Related Disorders, Coeliac/Celiac and Non-Coeliac Gluten Sensitivity Testing
Please click on the test links given below to see more detail, collection instructions, sample reports etc...
This medical field is evolving so fast it is sometimes hard to keep up! What we do know now is that there is a whole spectrum of gluten illnesses, not just coeliac disease (CD). CD is the most studied and is related to an autoimmune reaction in the gut, on the villi specifically, triggered by gliadin, one of the peptides in gluten grains. So far, so good.
We know that many people are mis or undiagnosed coeliacs, but we also now know that you can have other gluten related disorders (GRDs). In fact, gluten or gliadin IgE allergy, IgG delayed intolerance and non-coeliac gluten-sensitivity, which affects the neurological systems more than the gut, are probably much more prevalent.
Testing these disorders is also evolving, but we do now have a strategy for finding most of the hidden coeliacs and GRD sufferers previously told they had no problem with gluten and it was all in their heads!
First, before giving up gluten, you need to test for coeliac disease to rule it in or out. This is often negative because mainstream tends to look for gliadin 33-mer and transglutaminase antibodies linked to villi autoimmunity only. We know of plenty of others now and it seems daft to only look for the well-known ones.
I recommend you do Cyrex 3x testing as a minimum now to look for as many of the peptides and transglutaminases as you can. This is not perfect but this is so much better than what we've had up to now. The best way to start with testing, I think, is the Cyrex 2,3x and 4 bundle which saves you £100 - and most people end up doing them!
You can view all of the Cyrex tests here and the Cyrex FAQ here and a sample report here - they all look like this one but with the different analytes tested. Note: equivocal is taken as a weaker positive, not borderline.
I can do a standard 33-mer gliadin and transglutaminase test if you wish, but I find myself constantly saying: 'yes, but now test Cyrex 3 before you believe a negative!'
The Cyrex tests are ordered via the UK lab and drop-shipped for you to the US. The samples need centrifuging - pls see the FAQ for more on how to do this. Please also note: you must write your date of birth on the vials as we would do it normally in the UK/Europe as in 11/4/1987 for 11th April 1987 or your samples will be rejected. I have no idea why, but this is now Cyrex policy.
If you've given up gluten already...
You can still do Cyrex 3 if you've not been off long. See the FAQ below for specific timings etc. I do NOT recommend reintroducing gluten for testing - and neither do most of the experts I speak to - because of the potential for causing more damage. Instead, use the Gluten Gene Test.
Gluten Gene Testing
Gene testing can tell you what genetic pattern and therefore risk you have of developing a gluten related disorder (GRD); the genes have to be triggered or 'expressed' for you to develop the GRD. However, many people can put 2 and 2 together when they see their gene pattern and their symptom picture in context.
In mainstream, the HLA DQ2 and DQ8 genes are well-associated with coeliac disease and your doctor can look for those. DQ2 is the most predictive of CD risk. DQ8 is much less common. However, we are now finding that DQ1 and DQ3 are also predictive, more of NCGS or other forms of GRD. I introduced this test to the UK and look for all of the relevant genes on both A and B locations. It's the best you can get. It does need to be sent to the US, so do bear that extra cost in mind.
You can read all about the gene test and order it here. This will send you to the GFS who get the test done for us by Labcorp. When you order, if you put my email firstname.lastname@example.org instead of yours, we will then get the results sent to us, analyse them and email them to you with our thoughts on what they mean and what to do about them. You can put your own address if you prefer but then you don't get our thoughts: up to you! GFS are meant to send them to us but rules now state they have to send it to whatever email you put on your form. This is what your gene results might look like. All results come with a full analysis and explanation in writing and video:
Gluten Sensitivity Gene Analysis Results
|Test Date||Molecular Analysis of DQA1 Genotype||Gluten Sensitivity Positive|
|Molecular Analysis of DQB1 Genotype|
Genetic Analysis of your HLA-DQ genes reveals that you have four positive gene alleles for gluten sensitivity. If you have one gluten sensitive gene allele, then your offspring have a 50% chance of receiving the gene from you, and at least one of your parents passed it to you. Having two copies of a gluten sensitive or celiac gene allele on the same gene, means that each of your parents and all of your children (if you have them) will possess at least one copy of the gene. Two or more copies also mean there is an even stronger predisposition to gluten sensitivity than having one gene and the resultant reaction to gluten may be even more severe. This is important to understand because if you have children or family members with unexplained illness, they should be tested as early as possible to rule out gluten sensitivity.
Gluten Free Diet Testing
It is now believed by some, including me from personal and clinical experience, that many coeliacs and indeed GRDs generally, are not healing because they are reacting to other foods that cross-react with gluten/gliadin so the body gets confused and reacts in the same as it would to the gluten. Dairy and other grains are the most common.
Cyrex 4 has been designed specifically to help you find if you have antibodies to the cross-reactive foods and, usefully, also to some of the most common GF diet substitute foods. I would then follow that up with Cyrex 10, a much larger food panel; the best I have seen in a long time. See the leaflet here on this. There is also a useful video here.
You can also now do:
Cyrex 10C, which includes Arrays 3, 4 and 10. This has a good saving on doing the tests separately for you. This is the best value test by a long run if you're going to have 3, 4 and 10 done anyway at some point, although the 10-90 options below will help you spread the cost if need be.
Array 10-90, which includes the top 90 allergens from the Cyrex 10.
Array 10-90X, which you can do as an add-on later if you want to do the other 90 allergens from the Array 10 panel.
Array 10-90P which includes 3, 4 and 10-90. Again, a good saving here doing the tests separately, although do remember that doing the 10C works out much cheaper. I do try for you!
Array 14, a bundle of Cyrex 2 (leaky gut), 3 (the gluten panel) and 4 (cross-reactives and substitute foods)
Here is a useful rundown of the various Array 10 panels for you.
See also the Allergy Tests section for my thoughts on how to test effectively for food reactions. For antibody tests, you need to be eating the foods, remember so an ALCAT is better if you aren't.
In general, I would combine Cyrex 4 and 10 or a Cyrex 10-90P with an ALCAT test for non-antibody reactions for the best chance of finding your healing diet. The absolute ideal would be to do Cyrex 10C plus an ALCAT - sadly, out of reach for most people.
One thing to remember is that, if you suspect your immune antibody production is low ie. your IgA or SIgA has been low at some point or you have immune issues such as chronic infections, frequent colds, autoimmunity, chronic fatigue or multiple sensitivity, it can often be a good idea to do a Total Immunoglobulins test before any antibody test like Cyrex. If you are not producing much, you could get false negative results. I've put a Total Immunoglobulins test on this section for you in case. This wouldn't affect the ALCAT test as that doesn't measure antibodies.
Gluten Treatment Testing
Leaky Gut or Blood-Brain Barrier
Next, you need an idea of what your specific GRD is up to in the body so you can devise a way to combat it. In essence, you can check the damage gluten has done to your gut with Cyrex 2. Gluten is known to affect the functioning of the tight junctions in the gut wall, which makes you 'hyper-permeable' or leaky in common parlance.
I think if you have sensitivities to other stuff as well as gluten, you can possibly assume and treat this without testing, although it can give some useful targetting info on whether the leakiness is more about food or bacterial infection. It also gives you a progress marker you can monitor.
Similarly, you can test now for a leaky blood-brain barrier using Cyrex 20. We know that most GRDS are actually affecting the brain and nervous system (think: brain fog, movement disorders, migraine, anxiety, ataxia, depression etc). Sometimes, seeing this leakyness on paper answers a lot of questions. Again, it can act as a progress monitor.
You can also now check for evidence of leaky gut and SIBO in the small intestine. Cyrex 22. This is very different to the breath test in that it is looking for antibodies to bacterial cytotoxins released in SIBO rather than the gases we produce. It also looks for evidence to see if the cytotoxins have caused a leaky gut. You can see more info on this sheet here.
We know that gluten is the only common denominator found so far in autoimmune disorders, which is really exciting info! Coeliac disease is an autoimmunity attack on the absorptive villi in the gut, hence the problems that come with CD illness. But that is what we know and have studied. Other people have autoimmune thyroid or adrenal issues, ovarian attack (infertility is common in GRDs), skin diseases, reactive arthritis, psoriasis etc etc. The list goes on.
First, check if autoimmune disease markers are present. Use Cyrex 5 for a really comprehensive autoimmune screen (you can see an interpretation table of what each antibody means etc here), Cyrex 6 for diabetes, Cyrex 7 or 7X for the neurological autoimmunity screen, Cyrex 8 for joint autoimmunity and Cyrex 20 for blood-brain.
Pathogens and other triggers
Next, consider if pathogens are causing your issues. Cyrex 12 assesses IgG immune reactivity to pathogens that are documented triggers or exacerbators of autoimmunity and chronic disease. The test looks for IgG antibodies to various pathogens including oral pathogens, gastrointestinal parasites, bacterial and stealth pathogens, environmental moulds (molds), viral pathogens and tick-borne pathogens - you can see all of them here. If an IgG antibody is present, it doesn't show a current infection, but it suggests there is a hidden or latent pathogenic problem that may well be causing you problems or acting as a trigger.
It can also be a good idea to consider levels of known toxic chemicals in your system. Could you have a high levels of something like glyphosate (Round Up) in your system that is triggering cross-reactivity to organs and tissues maybe or messing about with your gut flora, hormones etc? To check that, see the Glyphosate and GPLTOX tests here and maybe also check Cyrex 11 for any clues that you are immunologically reacting to any of the most common ones. In other words, you can now check for presence and immune reaction to them.
For much more on this whole complex field, do read the TGF site in Resources above, and download the Gluten Plan for full testing and treatment protocols. You can read much more about the Gluten Plan here.
Testing Hints & Tips:
Q: Do the Cyrex samples need centrifuging?
A: Yes. Please see the FAQ for more details on having blood taken locally. With the Cyrex kits only, I asked Regenerus if they would centrifuge the samples for us. They said yes:
Yes we can, the only catch is that it does have to get to us within 24 hours. Our UPS shipping can do that as long as the patient can get it picked up the same day as the blood draw. So if that can be guaranteed, then your patients can send the whole blood sample to us for centrifuging. We include a UPS shipping label in with the test kit which patients will pay for if they use it. So, you would need to arrange to have your blood sample taken first thing and have arranged for UPS to collect it/you drop it off to UPS that same day, preferably in the morning, and pop a VERY CLEAR note in and/or have arranged beforehand for Regenerus to centrifuge the sample for you.
Q: If I have one Cyrex test done, can I have another one done on the same blood sample?
A: Yes, you can. You can add on multiple tests within the first 21 days. They then freeze your blood sample for 90 days, so between 21 and 90 days you can add on other tests once only and they will be done once the sample has thawed. This is most commonly done, for example, if you have done Cyrex 3, found a problem and then want to test the cross-reactive foods with Cyrex 4 and/or the predictive autoimmune antibodies Cyrex 5. We just ask them to use the same sample. I wish all the labs would do this!
Q: Can I do the Cyrex tests if I am off gluten?
A: It depends. If you have been off it for less than a couple of weeks, you can still test reliably. The advice is: if you have been off it for fewer than 10 days and you were eating it regularly before, wait 25 days after your last ingestion and then do Cyrex 3.
If you have been off it for more than a few months or even years, doing the test can actually show you if you are still producing antibodies and therefore if you diet is good enough to heal. If you find something, it means you are likely still consuming some gluten hidden somewhere or a cross-reactive food. That is crucial knowledge for healing.
Q: Can I do the Cross-Reactive Foods test, Array 4, or the Food Screen, Array 10, if I am off some of the foods?
A: Yes, this is the same as above. For antibody tests, you need to be eating the food or have done recently. Follow the same guidelines if you wish to reintroduce a food to test.
Q: Can I continue or go back onto the foods safely if the antibody tests are negative?
A: For gluten, you need more tests to know whether that is safe. The most common reaction is an antibody one but there is a possibility that you have a different mechanism. If all antibodies for gluten are negative, that's a great sign, but do an elimination diet check and the gluten gene test as a double check before you introduce it.
For the cross-reactive foods, you may not yet be as far as producing an antibody, so I advise an elimination diet as a double-check to be certain.
Q: Can children do Cyrex tests?
A: Yes, it is fine for under 16s. For small children, the lab says: "No restriction on age. If they are old enough to be eating gluten, they can be tested. The difficulty is generally taking the blood."
Q: I have got saliva and blood vials in my test kit. Is that right?
A: Yes, there is one test kit for all the tests so just use the one you need and discard the other, or keep it for later in case you need a blood test further on.
Q: I have gone wrong with my saliva test as I ate something before it. Can I rinse it out?
A: No, you need a new vial. Please contact me or Regenerus direct to request one.
Q: Will I need follow-up tests?
A: The best way of finding out your progress is to repeat your test so you know you are on the right diet, protocol and path to heal.
Q: Is there any logic to sequential testing with the Arrays? Do the results of one test provide direction for the other tests?
A: Yes. There are logical sequences to testing. Ideally we recommend ordering Arrays 2, 3, 4 and 5. Another option is to start with Arrays 2 and 3 and depending on your results, add Array 4 and 5 if necessary. The lab will freeze your blood and you can order additional test(s) within 90 days. I have added a combination test of the most frequent food screen now - arrays, 3, 4 and 10.
Q: Are there any medications, foods, conditions, or other factors that could interfere with the results of a Cyrex test?
A: Yes. While Cyrex is unable to provide an exhaustive answer to this question due to the interactive complexities and varieties of medications and patient circumstances, the following has been noted:
Q: How soon after finishing steroids can a patient do Cyrex testing?
A: 60 days. It takes this period of time for the medication to clear the system and allow the normalized production of antibodies, required for immune testing, to resume.
Q: What is the difference between the Lactulose/Mannitol test and Cyrex’s Intestinal Antigenic Permeability Screen™ (Array 2)?
A: The Lactulose/Mannitol test is an assessment of nutrient absorption. It looks for the passive absorption of micromolecules (mannitol) and relative permeability to lactulose. For the test to be effective, intestinal dysregulation must be present. Cyrex’s Intestinal Antigenic Permeability Screen™ assesses gut barrier damage by measuring antibodies to barrier proteins. It can therefore detect barrier damage long before there is dysregulation in absorptive function. This makes Cyrex’s Intestinal Antigenic Permeability Screen™ preferential for early detection and preventative care.
Q: How long does it take to see reductions in the antibodies to the lipopolysaccharides, actomyosin, or occludin/zonulin after the gut barrier is restored?
A: Antibody levels decrease on a curve and not in a line. Based on patient populations, initial significant decreases—after no exposure—can be seen in two weeks for IgA, four weeks for IgM, and six weeks for IgG. Lower levels can remain longer after this initial reduction. IgG can be found in some patients up to one year after exposure.
Q: If someone recently had an infectious gastroenteritis, would this temporarily cause a leaky gut and give a positive result to the Array 2?
A: In a person with infectious gastroenteritis, you may detect leaky gut. It is recommended to wait at least four weeks after completion of treatment before ordering Array 2.