Testing to Diagnose Celiac Disease

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Testing to Diagnose Celiac Disease

Those looking for a definitive answer whether or not they have Celiac Disease (CD) or gluten sensitivity will be faced with many different testing options. Please be advised that the field of testing is ever changing, and you can find pros and cons to each test currently available. Here we provide you with the basic information, clinical highlights and accuracy considerations for a variety of different types of tests that can be ordered from your doctor or independently.

** GFP highly suggests you consult with your primary care physician on testing options. 
All diagnostic tests need to be performed while you are on a gluten-containing diet**

Research from the Center for Celiac Research at the University of Maryland’s School of Medicine (in 2011) has proven that gluten sensitivity is different from CD both at the molecular level and in the immune system response. It is now understood that gluten sensitivity and CD are part of a spectrum of gluten-related disorders. There is currently no widely accepted diagnostic lab test for gluten sensitivity, however it can be self-diagnosed with an elimination diet once celiac disease and wheat allergy has been ruled out.

The following tests are used to diagnose CD:

Blood Test

Blood tests can be divided into identifying two different types of antibodies: those that are “anti-gluten” and those that are “anti-self,” or autoimmune. The anti-gluten antibodies are the anti-gliadin IgG and IgA. Ig stands for “immunoglobulin” or “antibody”. The “anti-self” antibodies are anti-endomysial IgA and anti-tissue transglutaminase IgA. The tissue transglutaminase IgA antibody is often abbreviated as “tTG”.

A person needs to be eating a diet that includes foods with gluten - such as breads and pastas - when the test is taken. If a person stops eating foods with gluten before being tested, the results may be negative for CD even if the disease is present.

While some say current blood tests for CD are very accurate, particularly when tTG and anti-endomysial antibodies are elevated, more recent findings estimate blood testing is only 27-30% accurate because of false positive and false negative findings, especially if there is only partial villous atrophy versus severe damage to the villi typically found in end-stage CD.

Another issue with the celiac blood test is that it does not account for those with IgA deficiency, which occurs 10 to 15 times more commonly among people with celiac disease than the general population. Patients with IgA deficiency will lack IgA antibodies, so this blood panel shows up negative. The tests to consider for these patients are dGP (deamidated gliadin peptides) or the IgG TTG antibody.  Recent studies have shown that the dGP assay can effectively identify patients that have Non-responsive celiac disease (NRCD).  When patients have persistent villous atrophy despite following a gluten-free diet.

Your physician will determine which blood tests to perform.  Of the available blood tests that help screen for celiac disease, no one test is ideal.  A typical blood panel may consist of the following:  

  1. Anti-endomysial antibodies (EMA) - IgA
  2. Anti-tissue transglutaminase antibodies (tTG) - IgA 
  3. Total serum IgA level
  4. Deamidated gliadin peptide (DGP) antibodies

According to the NIH Consensus Conference on celiac disease, a separate panel has suggested that the antigliadin antibody (AGA) tests are no longer routinely recommended because of their lower sensitivity and specificity results.

Blood tests are typically used to indicate who needs to have a biopsy, not for the diagnosis of CD.

Some celiac experts are now recommending an intestinal endoscopy, even if antibodies are negative, when the following factors are present: 

  • Gastrointestinal symptoms such as abdominal pain or discomfort, diarrhea or weight loss.
  • Severe (unexplained) premature osteoporosis, and/or
  • Abnormal lab tests, such as iron deficiency or elevated fecal fat.

Intestinal Biopsy

The diagnosis of CD requires abnormal microscopic findings in small intestinal biopsy specimens – therefore this test has been considered “the gold standard” in diagnosing CD. If blood tests and symptoms suggest CD, a biopsy of the small intestine is performed to confirm the diagnosis. During the biopsy, the doctor removes tiny pieces of tissue from the small intestine to check for damage to the villi. To obtain the tissue samples, the doctor eases a long, thin tube called an endoscope through the patient's mouth and stomach into the small intestine.  According to David A. Johnson, MD, from Eastern Virginia Medical School, it is recommended that a minimum of 4 or more biopsy samples be taken from the second and third portions of the duodenum and 1 or 2 from the duodenal bulb and interpreted by an experienced pathologist.

  • Biopsies are helpful when blood tests are negative but symptoms are present. While endomysial (EmA) and tissue transglutaminase (TTGA) antibodies are detectable in most cases where villous atrophy is present, 5-10% of patients lack these antibodies. Therefore, when the facts are suggestive of CD, perhaps with a family history or strongly suggestive symptoms; biopsy is the only way to make the diagnosis.
  • A follow-up biopsy can also give an indicator of progress, as only 40% of people have complete recovery after 12 months gluten-free living. EmA and TTGA disappearance is only a marker of how successful gluten exclusion has been and is not a reliable indicator of bowel recovery, which is important for assessing nutrient absorption.

A new study published in the American Journal of Gastroenterology in 2014 suggests that the blood tests tTg and DGP antibodies in combination may be useful markers of mucosal healing for children with celiac disease on a gluten-free diet.  Which may question the need for routine biopsy. 

Dermatitis Herpetiformis Skin Testing

Dermatitis herpetiformis (DH) is an intensely itchy, blistering skin rash that affects 15 to 25 percent of people with CD. The rash usually occurs on the elbows, knees, and buttocks. Most people with DH do not have the digestive symptoms common to celiac disease. DH is diagnosed through blood tests and a skin biopsy. If the antibody tests are positive and the skin biopsy has the typical findings of DH, patients do not need to have an intestinal biopsy. Both the skin disease and the intestinal disease respond to a gluten-free diet and recur if gluten is added back into the diet.

Genetic Testing

Genetic testing for celiac diseaseCD tends to occur in families and therefore individuals with family members who have CD are at increased risk of developing the disease. Genetic susceptibility is related to specific HLA markers. More than 97% of individuals with CD in the United States have DQ2 and/or DQ8 HLA markers. Some of these HLA genes can be identified by using a sample of blood or cells taken from your mouth by swabbing the inside of your cheek.

Tests that detect HLA DQ2 and DQ8 genes can suggest CD, but they cannot confirm a diagnosis, since 35 to 40 percent of the overall American population carries these genes, but only a small portion of people with these genes will ever have CD. Negative findings for HLA-DQ2 or HLA-DQ8 can rule out current or future CD in patients. In other words, those that test negative for the HLA-DQ2 and DQ8 genes (including both alpha and beta subunits) do not need further follow up.Those with “Latent CD”  might be asymptomatic in their younger years, but later in life may develop symptoms if certain markers are present, including insulin resistance, vitamin D deficiency, chronic inflammation and infections and/or viruses, all of which can trigger the expression of the HLA genes.

Saliva and Stool Testing

Other ways to test for CD include stool test and salivary tests. While gaining some momentum in recent studies (Journal of Pediatric Gastroenterology & Nutrition, January 2011) they are not widely accepted as diagnostic within the medical community. Many of these tests can be ordered on-line and performed at home without a doctor ordering the test. 

For example, one method uses stool rather than blood as the testing substrate based on the assertion that immunologic reactions to gluten proteins occur in the intestinal tract, and not in the blood. Salivary tests may be used to identify the presence of genes associated with celiac disease or to measure various hormones, antigens and antibodies. 

We suggest that you check with your primary care provider before ordering these tests.

Elimination/Provocation Diet

An elimination/provocation diet could be considered the gold standard for “self-diagnosis.” The basis of this diet involves removal of gluten completely for three weeks then adding it back in systematically to see if symptoms return. If symptoms dissipate while gluten is out of the diet, and then return when re-added, it’s likely you are having a problem with gluten somewhere along the celiac-sensitivity continuum. Click here for for more information on the elimination diet


Harrison MS, Wehbi M, Obideen K: Celiac disease: More common than you think. Cleve Clinic J Med 2007;74:209-215

Dickey W, McMillan SA, Hughes DF. Sensitivity of serum tissue transglutaminase antibodies for endomysial antibody positive and negative coeliac disease. Scand J Gastroenterol 2001; 36: 511-4.

Dickey W, Hughes DF, McMillan SA. Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery. Am J Gastroenterol 2000; 95: 712-4.

Dr. Sheila Crowe, a professor in the division of gastroenterology and hepatology in the department of medicine at the University of Virginia. For the New York Times, January 13, 2010. “Genetic Testing for Celiac Disease”.

Abrams JA, Diamond B, Rotterdam H, Green PH. Seronegative celiac disease: increased
prevalence with lesser degrees of villous atrophy, Dig Dis Sci. 2004 Apr;49(4):546-50

Tursi A., Seronegative Coeliac Disease: a Clinical Challenge. BMJ 26 April, 2005

Rostami, K., Unforgiving Master of Non-Specificity and Disguise, BMJ 27, April 2005

Lebwohl, Green P., Screening for Celiac Disease. N Engl J Med Oct.23 2003,1673-4

Spatola, Kaukinen, Collin, et al, Persistence of Elevated Deamidated Gliadin Peptide Antibodies on a Gluten-Free Diet Indicates Nonresponsive Coeliac Disease, Aliment Pharmacol Ther. 2014, 39(4):407-417