Cyrex Array Three: A Better Test for Gluten Sensitivity?

laboratory technician picks up a test tube with a human blood sample
The new Cyrex 3 test helps identify both celiac disease and non-celiac gluten sensitivity. David Silverman/Getty Images News/Getty Images

Laboratory blood tests offer clinicians screening tools to help diagnose sensitivity to gluten -- key factors when considering a diagnosis of Celiac disease, or non-Celiac gluten sensitivity. Celiac disease and gluten sensitivity are associated with an increased risk of autoimmune diseases, including thyroid conditions like Hashimoto’s disease and Graves’ disease.

Cyrex Laboratories' Array 3 Wheat/Gluten Proteome Reactivity and Autoimmunity test panel is a unique test to help identify gluten sensitivity and autoimmune reactivity.

 Cyrex is a clinical immunology laboratory specializing in functional immunology and autoimmunity. 

We caught up with Ms. Jama Lambert, Director of Education at Cyrex Laboratories, to talk about the test.

Celiac Disease or Non-Celiac Gluten Sensitivity?

Celiac disease (CD) is a confounding, frustrating condition that occurs when your immune system identifies gluten as an antigen. The resulting inflammatory response from your immune system can bring on a cascade of symptoms and potential tissue damage.

Symptoms similar to those produced by Celiac disease are experienced with non-Celiac gluten sensitivity (NCGS).  There is an important difference between symptoms caused by an immune response—or a physical intolerance for gluten products.  

There are already several Celiac screening tests on the market.  Two common ones - the tTG-IgA test and the DGP IgA and IgG -- measure antibodies synthesized by the immune system when antagonized by different proteins.

  The first, TTG, is tissue transglutaminase, an enzyme released in the small intestine during an active autoimmune response.  The second, DGP, is a protein found in gliadins and is abundantly present in cereal grains.

Symptomatic patients who react to proteins outside this narrow band can receive false negative results and be misdiagnosed—leaving them at risk for untreated symptoms of an autoimmune reaction to the gluten they continue to consume.

How Does the Cyrex 3 Array Differ From These Two Tests?

According to Cyrex's Jama Lambert:

The standard Celiac screening test usually includes tissue transglutaminase – 2 IgA.  Cyrex Array 3 contains tTG2 IgA as well as tTG2 IgG.  The DGP measure of deamidated gliadin is one of the of the gluten proteins assessed on the Array 3.  Studies have shown that 50 percent of celiac patients do not react to this one protein from wheat. Instead, they react to protein that is not assessed.  If measuring only this one protein from wheat, such a patient would get a false negative result.

Wheat is made up of over 100 proteins, yet the standard blood work for Celiac disease assesses only one protein from wheat.

Since 2002, researchers have called for an expansion of the assessment for gluten reactivity because 50 percent of Celiacs do not react to that one protein.  Papers, by by Camarca, Vader, and Vojdani et al., outline the proteins of wheat to which Celiac patients reacted rather than deamidated alpha-gliadin-33-mer.

Cyrex Laboratories looked at what those researchers were finding to be the most antigenic to humans and put those proteins on Array 3.  By assessing multiple proteins from wheat, Array 3 has increased sensitivity for identifying wheat/gluten reactivity.

According to Cyrex, then, the Cyrex Array 3's difference is the ability to identify gluten reactivity and effectively measure antibody production against multiple—in this case, eight—wheat proteins, peptides, and enzymes.

Can the Array 3 Panel Replace Multiple Screening Tests?

According to Lambert, the Array 3 tests for the traditional wheat protein and transglutaminase evaluated in other tests, plus it provides an expanded look at other gluten family proteins, additional transglutaminases, and markers of known triggers of autoimmunity/tissue damage.

Array 3 can help a practitioner differentiate between possible Celiac disease and non-celiac gluten-sensitivity.  Not every person’s gluten-reactivity manifests as Celiac disease—some patients have dermatitis herpetiformis or psoriasis, while others may have gluten ataxia, and assessment of the various transglutaminases helps to identify these types of reactivity.

Array 3 includes transglutaminase-3 and transglutaminase-6, respectively as well as two additional markers that can identify triggers of autoimmunity and intestinal damage, namely Wheat Germ Agglutinin and the Gliadin-Transglutaminase Complex.

What About Non-Celiac Gluten Sensitivity?

According to the National Foundation for Celiac Awareness (NFCA), about 18 million people suffer from non-Celiac gluten sensitivity, about six times as many people who suffer CD.  There is no known causal mechanism for either condition.

The purpose of Array 3, according to Lambert, is: help clinicians identify gluten-reactivity in their patients.  The clinician can use these test results in conjunction with other pertinent clinical information to determine if the patient has possible Celiac disease, non-celiac gluten-sensitivity, autoimmune reactivity and/or intestinal damage.”

According to Dr. David Perlmutter, MD, FACN, and author of the New York Times’ best seller Grain Brain: 

The Cyrex Array 3 offers the most comprehensive analysis available for determining gluten sensitivity, this array has proven incredibly valuable in my practice by providing in-depth information about an issue that has wide clinical implications

Understanding the Fine Print

It's important to acknowledge that the issue of non-celiac gluten sensitivity is controversial in some medical circles. Some experts believe that it is common, others say it's rare, and yet others believe that these symptoms are instead evidence of a sensitivity to FODMAPs

While the Cyrex Array 3 shows promise, it's also important to note that the Array 3 is not a definitive diagnostic tool.  A healthcare provider can use the results of Array 3, along with other clinical information, to make an assessment about the possibility of non-Celiac gluten sensitivity, and/or autoimmune reactivity.

If you want to learn more, or are interested in using the Array 3, here are some tips:

  • Before you seek out/have/pay for this test, make sure that your physician feels that this test will be helpful in your diagnosis. [Note: licensed medical doctors (MD), osteopathic physicians (DO), naturopathic physicians (ND), or nurse practitioners (NP) are almost always preferable to chiropractors for diagnosing and treatment autoimmune, thyroid and celiac/gluten-related health conditions.] 
  • The test is available through Cyrex Laboratories, where your doctor can open an account to order the test for you. 
  • Patients obtain the collection kit from their ordering physician with a requisition form.  The patient obtains a blood draw from a lab.  Unless the facility is under contract with Cyrex, the fee for the blood draw is paid by the patient.
  • Results are delivered to your doctor through their Cyrex account, and your doctor will discuss results with you directly. 
  • Cyrex Laboratories does not currently have contracts with any healthcare providers, including Medicare, so patients are responsible for the costs. (As of summer 2015, the Array 3 test costs $325.) Upon payment, you can submit your receipt to your insurance provider for potential reimbursement.

Tests like the Array 3, in conjunction with other screening tools and diagnostic procedures conducted by qualified physicians, may help you learn more quickly what you can do to regain your health and wellbeing. 

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