Gluten Sensitive? Coeliac? Cyrex Laboratory Tests may help pinpoint previously undiagnosed sensitivities

Nutritionist Christine Bailey discusses the Cyrex panels of gluten sensitivity related testing that have recently become available in the UK, and their value to those with autoimmune conditions, coeliac disease and gluten sensitivities.

Autoimmune diseases (A.I.D.s) arise from an inappropriate immune response of the body against substances and tissues normally present in the body. In other words, the immune system mistakes some part of the body as a pathogen and attacks its own cells. There are over 70 classified A.I.D.s. They include conditions such as coeliac disease (CD), Hashimoto's thyroiditis, Graves disease, rheumatoid arthritis, type 1 diabetes and multiple sclerosis. What is often overlooked is that autoimmune diseases are the third leading cause of morbidity and mortality in the industrialised world, surpassed only by cancer and heart disease (14). There are also many links to autoimmune conditions, CD and gluten sensitivity.

Practitioners such as myself have long been frustrated with the lack of sensitivity and specificity of many standard tests for gluten sensitivity and CD as well as wanting to use more sophisticated tests to pick up the presence of autoimmune antibodies long before signs and symptoms are present in clients. This could mean clients who have a family history of autoimmune disease can have their antibody levels measured to check susceptibility long term. Even if you have a genetic susceptibility it does not mean it is inevitable you will develop an autoimmune disease such as CD and making positive steps early may help reduce your risk.

So I am delighted that Cyrex Laboratory tests are now available in the UK through Regenerus Laboratories. For those of you who not familiar with Cyrex they are a clinical immunology laboratory (based in Phoenix) specializing in autoimmunity. Cyrex offers multi-tissue antibody testing and specialize in gluten sensitivity, cross reactivity and related testing.

Difficulties with Current Gluten Sensitivity Testing

Standard blood tests for CD are variable in accuracy dependent on the degree of villous atrophy present. Gluten has to have significantly destroyed the gut wall for current blood testing to be effective. Yet research shows us that for every gluten sensitive patient with the symptoms of an enteropathy (classic coeliac disease), there are eight with no GI symptoms (1,2). While genetic testing (HLA DQ2/8) is available this only tells us something about probabilities: it does not indicate actual intestinal damage or gluten mediated immune reactions. Faecal antibody tests, although more accurate than blood antibodies, are not readily available in the UK.

And here lies the difficulty faced by clients. They know they don't feel great when eating that bagel or sandwich and yet the doctor's standard blood tests for IgA anti-transglutaminase or anti-endomysial antibodies come back negative. In other cases the anti-gliadin, or anti-deamidated gliadin antibodies, may come back positive but the doctor does not consider it a problem because the tissue antibodies are negative.

There is another, often overlooked problem with the standard tests. When someone has gluten sensitivity, the gluten molecules in wheat, barley and rye are not digested sufficiently and remain as large peptides. It is these peptides that trigger an immune response. The current blood test only tests for one peptide of gluten – gliadin (the 33-amino acid chain Gliadin MER 33). However there are many putative peptides of gluten: one study found over 60 (3). Research suggests only about 50% of coeliacs have antibodies to the gliadin peptide – the rest don't but they do have antibodies to other gluten peptides (4). So a standard blood test only looking for gliadin peptide antibodies could result in a false negative. The problem here is not with the client. It is the test and its lack of specificity and sensitivity.

Introducing More Robust, Comprehensive Testing – The Cyrex Tests

CD is known to be one of the most common lifelong diseases in both Europe and the US (5). Its prevalence is estimated at 1% of the population (one in 100 people) (6). This equates to three million Americans and 620,000 people in the UK. However it is estimated that 78% of sufferers don't realise they have CD (7). While gluten sensitivity and CD are now recognised as two distinct "clinical entities" they have the same environmental trigger – gluten – and share many similar symptoms.

It has been demonstrated that for gluten-sensitive patients, eating gluten will cause an inflammation response in the intestines, and often in other parts of the body (8,9). It's therefore conceivable that gluten could be doing damage and causing constant, low-grade inflammation without clients even knowing it.

It is also now widely recognised in research that the peptides of gluten found in wheat, rye and barley may detrimentally affect any tissue in the body and are not restricted to the intestines The range of conditions where gluten sensitivity has been implicated is wide and diverse. From the skin (dermatitis herpetiformis, psoriatic arthritis, alopecia areata etc.), to muscles (inflammatory myopathies), the brain (gluten ataxia, schizophrenia, anxiety, depression, ADHD etc.), nerves and so on. Pathology to gluten exposure can occur in multiple systems without evidence of intestinal damage (10,11). To complicate matters other foods (even gluten free foods) can react in certain individuals in a similar way as gluten (12). This 'cross reactivity' may explain why some people adopting a gluten free diet still don't experience good health and why gut healing does not take place (13).

Autoimmune diseases are not only the third leading cause of morbidity and mortality in the industrialized world (14) - they are also ten times more common in a gluten sensitive enteropathy than in the general population (15). Duration of gluten exposure is a key factor in developing other autoimmune diseases (16). The longer sensitive individuals eat gluten, the more likely they are to develop other autoimmune diseases. As antibodies tend to be elevated years before any symptoms of autoimmunity earlier identification might result in earlier treatment, better quality of life and an improved prognosis for these clients. Taking a preventative functional medicine approach it is important to identify as soon as possible whether antibodies are present rather than wait until the damage is extensive enough that there are obvious symptoms (17)

The New Generation Of Gluten Sensitivity Related Testing

The Cyrex lab tests are now available to the public through registered qualified practitioners such as myself exclusively through Regenerus Labs (see below). There are 9 panels and any of these tests can be used either on their own or in combination. Two of the tests are saliva, the others are serum. Kits are dispatched either to the practitioner or client. For full details on these panels contact Regenerus Labs (see below) or myself (see below).

Array 1: Gluten Intolerance.
A sensitive saliva test for coeliac disease and gluten sensitivity. Rather than a blood test this saliva test makes it ideal for young children. It also includes a thorough range of analytes: Secretory IgA, Gliadin IgA + IgM, Transsglutaminase IgA + IgM (celiac disease screening test). IgM antibodies are included in saliva in order to avoid the reporting of false negatives for an individual with IgA deficiency.

Array 2: Intestinal permeability.
The standard lactulose / Mannitol test is an assessment of nutrient absorption. For the test to be effective intestinal dysregulation must be present. Cyrex's panel assesses gut barrier damage by measuring antibodies to barrier proteins. This includes measuring antibodies against the tight junction proteins (zonulin and occludin) and antibodies to the actomyosin network. It can therefore detect barrier damage long before there is dysregulation in absorptive function allowing for early detection and intervention. This test can also be used to monitor the progress of an intestinal repair protocol.

Array 3: Wheat/Gluten Proteome Reactivity & Autoimmunity.
If the client is not already on a gluten-free diet, this is a highly sensitive test which looks at a wide range of gluten related grains/peptides that may be having a negative effect. A much more comprehensive panel than standard gliadin testing

Array 4: Gluten-Associated Cross-Reactive Foods and Foods Sensitivity.
This test is particularly beneficial for clients who react to gluten but are not improving fully on a gluten free diet. It includes 24 foods, 13 of which are known to be cross-reactive with gluten(18). Cross-reactive means the amino acid sequences are so similar that the immune system can react as if the patient is still eating gluten. The other foods are ones that are eaten frequently on a gluten-free diet or are often introduced only after a client begins a gluten-free diet. Foods that are not introduced as an infant often don't pass the immune system's oral tolerance test. This means it is possible to react to them the first time they are eaten even if there is not a permanent sensitivity reaction. It is recommended that cross-reactive foods are avoided for life like wheat. Clients testing positive for the other foods can be slowly introduced to these foods on a rotation basis once gut healing has taken place (array 2).

Array 5 Multiple Autoimmune Reactivity Screen.
This test is particularly valuable when screening for an autoimmune process in multiple areas of the body. Research has demonstrated that many antibodies tend to be elevated years before any symptoms of autoimmunity ever develop. This panel enables early diagnosis and an adoption of a preventative programme. This screen covers a diverse range of antibodies associated with particularly diseases – examples include colitis, gastritis, multiple sclerosis, autism, demyelinating diseases, lupus, PANDAS, Guillain Barré syndrome, rheumatoid arthritis, osteopenia, osteoporosis, diabetes, Graves' disease, Hashimoto's thyroiditis, gluten ataxia, hepatitis.

Cyrex Array 6: Diabetes Autoimmune Reactivity Screen.
A more specific panel for diabetes type 1 (Glutamic Acid Decarboxylase 65 (GAD 65) IgG + IgA Combined, Insulin + Islet Cell Antigen IgG + IgA Combined).

Cyrex Array 7: Neurological Autoimmune Reactivity Screen.
Myelin Basic Protein IgG + IgA Combined, Asialoganglioside IgG + IgA Combined Alpha + Beta Tubulin IgG + IgA Combined, Cerebellar IgG + IgA Combined, Synapsin IgG + IgA Combined.

Cyrex Array 8: Joint Autoimmune Reactivity Screen.
Arthritic Peptide IgG + IgA Combined, Collagen Complex IgG + IgA Combined, Fibulin IgG + IgA Combined.

Cyrex Array 9: Secretory IgA (Oral Fluid).
An ideal test for children being saliva to check sufficiency of SigA for mucosal immune support.

These panels provide practitioners with effective, research supported tests designed not only to address gluten sensitivity and related issues regarding cross-reactivity and intestinal healing but early identification of autoimmune processes throughout multiple body systems. As such they provide a valuable tool for practitioners in their quest to assist client's long-term health and wellbeing.

Cyrex testing is only available in the UK from Regenerus Labs to UK health care practitioners and nutritionists who are registered with Regenerus. Contact Regenerus Laboratories – tel 0333 9000 979 – or myself at www.advancenutrition.co.uk.

See also Christine Bailey's books on Amazon.

References

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2. Fasano A, Catassi C., Current Approaches to Diagnosis and Treatment of Celiac Disease: An Evolving Spectrum Gastroenterology 2001;120:636-651

3. Pastore L., et.al., Orally Based Diagnosis of Celiac Disease: Current Perspectives, J Dent Res 87(12):1100-1107, 2008

4. Camarca, A., et.al., Intestinal T Cell Responses to Gluten Peptides Are Largely Heterogeneous: Implications for a Peptide-Based Therapy in Celiac Disease, J. Immunol. 2009;182;4158-4166

5. Maki et. Al. (2003) Prevalence of Celiac Disease among Children in Finland NEJM 348; 2517-2524 June 19,2003

6. Rubio-Tapia et. Al. (2012) The Prevalence of Celiac Disease in the United States The American Journal of Gastroenterology , 31 July 2012 doi:10.1038/ajg.2012.219.

7. Steele et. Al. (2011) Diagnosis and management of coeliac disease in children. Postgrad Med J. 2011 Jan;87(1023):19-25. Epub 2010 Dec 3.

8. Olesen M, Eriksson S, Bohr J, Jarnerot G, Tysk C. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998. Gut, 2004; 53:346-350.

9. Gillet HR, Freeman HJ. Prevalence of celiac disease in collagenous and lymphocytic colitis. Can J Gastroenterol, 2000; 14: 919-921.

10. Gluten sensitivity: from gut to brain., Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D, Lancet Neurol. 2010 Mar;9(3):318-30

11. Hadjivassiliou M, Grünewald R, Sharrack B, Sanders D, Lobo A, Williamson C, Woodroofe N, Wood N, Davies-Jones A., Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics, Brain. 2003 Mar;126(Pt 3):685-91.

12. Alaedini et a. (2007) immune cross reactivity in celiac disease anti-gliadin antibodies bind to neuronal synapsin I J. Immunol 2007: 178:6590-6595

13. Rubio-Tapia et. Al. (2010) Mucosal Recovery and Mortality in Adults With Celiac Disease After Treatment With a Gluten-Free Diet Am J Gastroenterol advance online publication 9 February 2010; doi: 10.1038/ajg.2010.10

14. Arnson Y, Amital H, and Shoenfeld Y, Vitamin D and autoimmunity: new aetiological and therapeutic considerations, J of Immunology, 2005, 175: 4119–4126

15. Alaedini A, Okamoto H, Briani, C, Wollenberg K, Shill H, Bushara K, Sander H, Green P, Hallett M, Latov N, Immune Cross-Reactivity in Celiac Disease: Anti-Gliadin Antibodies Bind to Neuronal Synapsin I, The Journal of Immunology, 2007, 178: 6590– 6595.

16. Ventura A, Magazzú G, Greco L; SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. Gastroenterology. 1999;117:297–303.

17. Green P, Alaedini A, Sander HW, Brannagan III TH, Latov N, Chin R, Mechanisms underlying celiac disease and its Neurologic Manifestations Cell. Mol. Life Sci. 62 (2005) 791–799

18. Studies have identified cross-reactivity among gliadin and foods such as milk chocolate, dairy, rye, barley, Polish wheat,  spelt, yeast, oats, coffee, casein, whey protein powder etc  The response to some of these food allergens parallels the response to gliadin and might be relevant to the pathogenesis of Gluten- Reactivity and CD by increased mucosal permeability, resulting in elevated antigen reabsorption, which can trigger immune activation with elevated levels of IgA antibodies.
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