This site is intended to share the answers I found in my quest to understand celiac disease with family,  friends, and others who may be trying to find the answers I too have been seeking. This is a compilation of answers from various sources (clearly listed and linked prior to the quotes).

What tests can be run to diagnose celiac disease?

(Source: Beth Israel Deaconess Medical Center, Harvard Medical School Teaching Hospital: FAQ – How is celiac disease diagnosed?)

[It is important to note that one should not start a gluten-free diet before having these tests.]

 

• IgA-tTG and total IgA: Currently, the most frequently used test is IgA anti-tTG, or tissue transglutaminase.
The tTG IgA test will be positive (>19) in about 98% of patients with CD that have been on a gluten containing diet. We call this number the test’s sensitivity. The same test will come back negative (<20) in about 95% of healthy people without CD. We call this the test’s specificity.
• Total IgA: Your doctor may additionally check your total IgA level to determine if you have an IgA deficiency, which is a harmless condition that is associated with CD. If someone is IgA deficient, they may have a false negative result to their EMA or tTG tests. In this case, your doctor can order a DGP test. He/she could also order an IgG tTG test instead, although this is slightly less accurate than IgA tTG.
• DGP: (deamidated gliadin peptide) There are occasional individuals whose IgA-tTG results may be misleading. In this case, we recommend using a newer test, anti-DGP (IgG and IgA antibodies to deamidated gliadin peptide). It is similarly accurate to IgA-tTG and is useful for patients with IgA deficiency.
• EMA: Another blood test that your doctor may order is an EMA, or endomysial antibody test. This test is used less frequently than the IgA anti-tTG, but since it detects the same target antigen on a tissue section it can be just as accurate.
• AGA: Anti-gliadin antibodies, or AGA, were used in the past, but are typically not routinely checked now because they are much less accurate than tTG or EMA.
A doctor will look at the tissue under a microscope to determine whether there is damage to the intestine that is characteristic of CD.
If your doctor is still uncertain as to whether or not you have CD, s/he may order an HLA-DQ2 or HLA-DQ8 blood test. This is a genetic test that will help her/him determine whether or not you have CD.

 

What tests might be run to identify problems caused/influenced by celiac disease?

(Or some of these test results might lead to a diagnosis celiac disease.)

(Source: Beth Israel Deaconess Medical Center, Harvard Medical School Teaching Hospital: FAQ – How is celiac disease diagnosed?)

“Depending on the patient’s particular symptoms and medical history, a number of physical examinations and lab studies may be carried out to help identify nutritional deficiencies, electrolyte abnormalities or other health concerns.”

• Examination of the abdomen may reveal a bloated stomach due to swelling of intestinal loops with fluids and gas
• Signs of weight loss such as muscle atrophy (loss of muscle mass) or loose skin folds
• Orthostatic hypotension (a decrease in blood pressure when going from a seated or lying position to standing)
• Peripheral edema (a collection of fluids in the arms and legs)
• Bruising
• Dermatitis Herpetiformis (DH) (see section on DH)
• Cheilosis (severely reddened and cracked lips; most commonly seen at the corners of the mouth)
• Glossitis (inflammation of the tongue with formation of ulcers in the mouth)
• Peripheral neuropathy (decreased sensation or numbness in the fingers and toes)
• Physical exam findings related to hypocalcemia (Chvostek's sign: tapping on a specific area of the face results in twitching of the facial muscle; Trousseau's sign: inflation of a blood pressure cuff on either arm results in a "carpal spasm," seen as flexing of the wrist)
• Low iron levels are common. (Ferritin is generally the best test to measure iron stores., Iron)
• B12 and folate: Anemia due to deficiency in iron, folate and, in rare cases, vitamin B12 may be present.
• Vitamin D (25-OHD)
• Zinc
• Parathyroid hormone
• TSH (thyroid stimulating hormone)
• Potassium
• Serum calcium
• Magnesium
• Fat soluble vitamins (with diarrhea)
• Carnitine
• Albumin (protein stores) if malnutrition is suspected
• Cholesterol panel
Imaging studies including x-rays, CT scans, and a variety of other tests are rarely necessary in the diagnosis of celiac disease. However, they may be needed to rule out other disorders in cases where the diagnosis is uncertain or to assess for complications of celiac disease.
• X-rays of the small bowel can be taken after the patient swallows a substance known as barium. On the X-ray, the doctor may observe dilatation of the small intestine or an absence of the normal pattern of the small intestine due to destruction of the villi. Similarly, abdominal ultrasound has also been used to suggest the diagnosis of celiac disease but at this time imaging studies are not routinely recommended in the diagnosis and follow up of celiac disease.
• Bone density studies (also referred to as a DEXA scan) should be performed in those recently diagnosed with celiac disease. DEXA scans are usually recommended after 12 months of strictly following a gluten-free diet.

More on: Genetics (Gene Testing) (Beth Israel Deaconess Medical Center, Harvard Medical School Teaching Hospital)

Genetic FAQs

(Source: Beth Israel Deaconess Medical Center, Harvard Medical School Teaching Hospital: FAQs)

"HLA-DQ2 and HLA-DQ8 are the names of two genes which are part of the immune system and are able to stick to the gluten proteins. Every person with celiac disease (CD) has at least one of these genes. If your doctor is unsure as to whether or not you have CD, s/he can perform a simple blood test to determine whether or not you have one or both of these genes. If you do not have one of these two genes, your doctor can rule out CD. If you DO have one of these genes, it is possible that you have or may develop CD. Your doctor will need to perform more tests. You do not need to eat gluten in order to have the gene testing. Visit Genetics under Medical Management on www.celiacnow.org."
"The Human Leukocyte Antigen (HLA) genes are linked to many autoimmune diseases such as CD. Everyone has a copy from the mother and a copy from the father. These copies can come in different versions called alleles. The HLA gene alleles that predispose to CD are called DQ2 and DQ8. One may have DQ2 or DQ8 in one of the copies or in both. People who have only one copy of DQ2 or DQ8 have a risk of about 3% of having CD, whereas people who have two copies of either have a risk around 10%. 

"HLA types are actually combinations of genes so it is possible to be DQ2 positive even if neither of your parents has this gene. Overall though, at least 50% of children of parents carrying DQ2 or DQ8 will also have one of these. Almost all people with CD have at least one DQ2 or DQ8 copy. This is why genetic testing is so useful to rule out CD. Nevertheless, since 30-40% of the general population has at least one copy of DQ2 or DQ8, the gene test is not a good test to confirm CD. Visit Genetics under Medical Management on www.celiacnow.org."

 

What future testing options are being researched?

"Intestinal fatty acid binding protein (I-FABP) is a cytosolic protein that is release by necrotic enterocytes. I-FABP has previously been studied as a possible marker to evaluate mucosal damage. This protein has been proposed as a sensitive diagnostic test in the evaluation of ischemia in mechanical small bowel obstruction [42]. On the other hand, I-FABP has demonstrated a positive predictive value of 98% in children with a positive serological test for celiac disease [43]. I-FABP levels increased significantly after two weeks of gluten challenge, while lower levels of I-FABP were seen in individuals following two weeks on gluten withdrawal. I-FABP may be considered as a future diagnostic tool that could assist in the diagnosis of celiac disease." (Source: The present and the future in the diagnosis and management of celiac disease

 

Can some test results be negative and a person still have celiac disease?

One Interpretation:

(Source: The University of Chicago Medicine Celiac Disease Center)

What are the chances of having a high tTG and a negative biopsy—even though I have a child who was biopsy-diagnosed with celiac—and still being negative for the disease?

“It’s possible to be truly negative with these facts, especially if the tTG are only mildly elevated. Also check the more specific EMA test. If it’s positive, we would conclude you’re a potential celiac, which means the disease is simply waiting to explode, and we’d suggest a gluten-free diet. March, 2016”

(More about: Potential Celiac)

Another Interpretation:

Excerpts from: Alessio Fasano – “Spectrum of Gluten-Related Disorders: People Shall Not Live by Bread Alone”

(Alessio Fasano: the W. Allan Walker Chair of Pediatrics at Harvard Medical School;  Vice Chair of Basic, Translational, and Clinical Research and Division Chief of Pediatric Gastroenterology and Nutrition at the MassGeneral Hospital for Children in Boston – In 2000, the research team of Alessio Fasano discovered zonulin, which regulates the intestinal permeability. In 2003, he published the results of the epidemiological study that demonstrated the prevalence of celiac disease in the U.S. to be far higher than previously thought, at a rate of 1 in 133 persons. – https://en.wikipedia.org/wiki/Alessio_Fasano)

“If you go on a gluten free diet, that’s the landmark treatment of Celiac Diseaes, you prevent this interplay between the genes and the environment, and you completely revert the autoimmune process because these people will have no symptoms anymore, the antibodies that you use for diagnosis will go back to normal, and the damage of the intestine, that’s the landmark of the auto immune insult is gone.” …

“A matter of fact, contrary to the general wisdom, the most frequent way the disease presents itself nowadays is not diarrhea and thirty pounds weight loss.  The most frequent way the disease presents itself today is with anemia and with that chronic fatigue. Some people that are diagnosed with fibromyalgia or chronic fatigue syndrome, they… this is the most frequent way the disease presents itself.  Don’t be surprised that this can happen because iron is absorbed in the very few inches in the very early part of the intestine.  If that is gone, there is no backup.  There is no other way to bring iron in. If you don’t bring iron in, you develop anemia.  You can have only this few inches damaged, the rest is spared, the culpability of the intestine to digest the absorbed food stuff is untouched, but you develop the other symptoms.  So that should not be surprising.”

Celiac disease – a clinical chameleon

Gluten is misinterpreted as bacteria (28:00)

[Question asked at the end of his presentation:]

“Which test do you believe is the best marker, be it blood or be it biopsy?

**”In the past, the paradigm to make diagnose Celiac disease was to fulfil five criteria. You have signs or symptoms of Celiac disease.  You have the antibodies test positive. You have to have the HLA, genetically compatible.  You have to have the damage of the intestine show the auto immune attack.  And the symptoms, they need to go away when you embrace a gluten free diet.  Eighty percent of people with Celiac disease will fulfil all five criteria, but there are exceptions.  There are people who have no symptoms and yet they have Celiac disease.  There are rare ten percent of people that that may have Celiac disease with negative antibodies.  Extremely more rare, one percent of the people that can have Celiac disease without the problem HLA genes.  Ten, fifteen percent of the time that we do that we do an endoscopy, we don’t find the damage because either the diletion (??) is patchy or it’s too far for the endoscope to reach. And we know well that some people on a gluten free diet for months and months, the symptoms will not go away.  So there are exceptions.  And based on that, we propose, and now it’s been embraced by the scientific community, that if four out of the five criteria will do it.  So if you have signs or symptoms of Celiac disease, strongly positive antibodies, compatible HLA, you can go on a gluten free diet without doing endoscopy.  If the symptoms go away and the antibodies will go away on a gluten free diet, that diagnosis is confirmed even without the endoscopy.  But you have to fulfil four out of five criteria.”