Level 2
Blood Tests in Celiac Disease (CD)
KEY POINTS:
• Blood tests can be useful to help diagnose CD as well as to get a
general idea of how patients with CD are healing once diagnosed.
Blood Tests for Diagnosis
What blood tests are used to diagnose celiac disease?
There are two modern blood tests for celiac disease:
1) Tissue transglutaminase IgA antibody level (commonly referred to as "tTG")
2) Deamidated Gliadin Peptide IgA/IgG antibody level (commonly referred to
as DGP)
The most frequently used test is the tTG. It is accurate at detecting most people with
celiac disease on a gluten-containing diet.1 However, a minority of patients with celiac
disease (~2%) do not produce any IgA antibodies. This is a condition called IgA
deficiency and is generally asymptomatic but may be associated with increased risk of
some infections. A person with celiac disease who has this condition will generally test
negative with the tTG test regardless of celiac status. 2, 3
This is why doctors often also test for serum total IgA. It’s also one of the reasons why
the DGP test was invented. DGP can detect people with celiac people with IgA
deficiency because it can test for two types of antibodies (IgA and IgG) in only one test.
The person must be on a gluten-containing diet, however, just as the tTG test requires.
There is also an IgG tTG test but it is less accurate than the IgG DGP test. Conversely,
IgA tTG is more accurate than IgA DGP.
The Endomysial Antibody test (EMA) is an earlier version of the tTG test. It is not as
widely available as tTG and is more expensive than tTG. For these reasons, it is
seldom used these days.
The anti-gliadin antibodies (anti-gliadin IgA or IgG) are older tests with the lowest
accuracy among all the celiac blood tests. Considering the wide availability of
newer/better tests, their use for diagnosis of celiac disease is highly discouraged.4
Is there a blood test that can detect celiac disease in a person on a gluten-free
diet?
Unfortunately, we currently do not have any accurate tests for this situation. Genetic
testing may be able to rule out celiac disease in this situation but it cannot confirm it.
The only way to test for celiac disease in this context is to undergo a gluten challenge.1
o Gluten challenge: A patient suspected to have celiac disease but eating a gluten-
free diet is asked to eat a fixed daily amount of gluten (3 grams/day, about 2
slices of bread). If the patient develops symptoms that are not tolerable, the
challenge is stopped at 2 weeks. At that moment, the patient has a small bowel
biopsy taken and blood is drawn for tTG and DGP levels. If the patient tolerates
the challenge during two weeks then he/she continues eating the same amount
of gluten for an additional 6 weeks. A small bowel biopsy is then taken and blood
is drawn again for tTG and DGP levels. We know that it is an uncomfortable
situation for the patients and is not 100% reliable as some people take months of
gluten exposure to develop diagnostic changes in blood tests or biopsy. We are
working hard to develop new tests to shorten or avoid gluten challenges.5
Blood Tests for Health Maintenance
Once a patient has been diagnosed with celiac disease, he/she is advised to follow a
strict gluten-free diet for life.6 During and after the diagnosis, doctors may order follow-
up blood tests that can be important for:
1. Checking if the patient's small intestine is recovering from the injury; if the patient
is still exposed to gluten.
2. Screening for and following up on diseases and nutritional deficiencies
associated with celiac disease.1
Can blood tests indicate if someone with celiac disease is correctly following a
gluten free diet?
Once a person with celiac disease is on a gluten-free diet for at least 3 months, a doctor
commonly checks the antibody tests that were abnormal at diagnosis, namely tTG
and/or DGP. A significant drop in these antibody levels along with an improvement in
the patient’s symptoms is usually expected after at least 3 months on a strict gluten-free
diet.7
Nevertheless, to this day no blood test has been shown to be as good as an expert
dietitian assessment to check if someone is correctly following the gluten-free diet.8
Tests to detect gluten in the stool of people with celiac disease are under development
in order to assess for dietary adherence or cross-contamination of foods claiming to be
gluten-free.9
What tests are commonly used to check for diseases that are more common in
people with celiac disease?
There are other autoimmune diseases that are commonly associated with celiac
disease. Physicians may consider it appropriate to test for these at diagnosis or follow-
up.
Examples:
Disease Blood Tests
Thyroid disease 10,11 • Thyroid Stimulating Hormone (TSH)
• Thyroid Hormones (T3, T4)
• Thyroid antibodies (anti-TPO, anti-TSHR, anti-microsomal)
Liver Disease 12 • ALT
• AST
• Alkaline Phosphatase
• Bilirubin
What tests are commonly used to help better understand the nutritional status of
a person with celiac disease?
When celiac disease is active, many nutrients are not well absorbed from the gut.
Doctors and dietitians run blood tests to monitor the blood levels of key nutrients. If
these levels are found to be abnormal, they are monitored at least twice in the first year
after diagnosis and treated until they normalize, and then retested every 1-2 years. 1, 13-
16
Examples:
System involved / Common Symptoms Tests
Blood cells (Red) • Iron stores
− Fatigue o Ferritin
− Shortness of Breath o Iron Binding Capacity
o Serum iron
• Complete blood count (CBC)
o Red cell morphology
• Folic acid
• Vitamin B12
Bones • Vitamin D
− Higher risk of fractures • Calcium
• Parathyroid Hormone (PTH)
Brain and nerves • Vitamin B6
− Fatigue • Vitamin B12
− “Brain fog” • Carnitine
− Limb tingling
− Abnormal gait
General health • Copper
− Frequent respiratory infections • Zinc
− Frequent digestive infections
TAKE HOME MESSAGES:
1. The tTG and DGP antibody tests are the main blood tests to diagnose and
monitor celiac disease.
2. Anti-gliadin antibodies are no longer used to diagnose celiac disease.
3. A number of other tests are useful for detection of disorders related to celiac
disease and monitoring of nutritional deficiencies. These should be considered
on a case by case basis with your clinician.
References:
1) Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA, ACG Clinical
Guidelines: Diagnosis and Management of celiac disease 2013. Am J
Gastroenterol 108:656-676.
2) Chow MA, Lebwohl B, Reilly NR, Green PH Immunoglobulin
A deficiency in celiac disease. J Clin Gastroenterol. 2012. Nov-Dec;46(10):850-4.
3) Kumar V, Jarzabek-Chorzelska M, Sulej J, Karnewska K, Farrell T, Jablonska S.
Celiac disease and immunoglobulin a deficiency: how effective are the
serological methods of diagnosis? Clin Diagn Lab Immunol. 2002 Nov;9(6):1295-
300.
4) Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J
Gastroenterol. 2010 Dec;105(12):2520-4.
5) Leffler D, Schuppan D, Pallav K, Najarian R, Goldsmith JD, Hansen J, Kabbani
T, Dennis M, Kelly CP. Kinetics of the histological, serological and symptomatic
responses to gluten challenge in adults with coeliac disease. Gut. 2013
Jul;62(7):996-1004.
6) Haines ML, Anderson RP, Gibson PR. Systematic review: the evidence base for
long-term management of coeliac disease. Aliment Pharmacol Ther.
2008;28:1042 – 66.
7) Kaukinen K , Sulkanen S , Maki M et al. IgA-class transglutaminase antibodies in
evaluating the efficacy of gluten-free diet in coeliac disease. .Eur J Gastroenterol
Hepatol. 2002;14:311 – 5.
8) Leffler DA, Dennis M, Edwards George JB, Jamma S, Magge S, Cook EF,
Schuppan D, Kelly CP. A simple validated gluten-free diet adherence survey for
adults with celiac disease. Clin Gastroenterol Hepatol. 2009 May;7(5):530-6.
9) Comino I, Real A, Vivas S, Síglez MÁ, Caminero A, Nistal E, Casqueiro J,
Rodríguez-Herrera A, Cebolla A, Sousa C. Monitoring of gluten-free diet
compliance in celiac patients by assessment of gliadin 33-mer equivalent
epitopes in feces. Am J Clin Nutr 2012 Mar;95(3):670-677.
10) Meloni A, Mandas C, Jores RD, Congia M. Prevalence of autoimmune thyroiditis
in children with celiac disease and effect of gluten withdrawal. J Pediatr. 2009
Jul;155(1):51-5.
11) Metso S, Hyytiä-Ilmonen H, Kaukinen K, Huhtala H, Jaatinen P, Salmi J, Taurio
J, Collin P Gluten-free diet and autoimmune thyroiditis in patients
with celiac disease. A prospective controlled study. Scand J Gastroenterol. 2012
Jan;47(1):43-8.
12) Casella G, Antonelli E, Di Bella C, Villanacci V, Fanini L, Baldini V, Bassotti G.
Prevalence and causes of abnormal liver function in patients with coeliac
disease. Liver Int. 2013 Aug;33(7):1128-31.
13) Tikkakoski S , Savilahti E , Kolho KL . Undiagnosed coeliac disease and
nutritional deficiencies in adults screened in primary health care. Scand J
Gastroenterol. 2007;42(1):60 – 5.
14) Hallert C, Grant C, Grehn S et al. Evidence of poor vitamin status in coeliac
patients on a gluten-free diet for 10 years. Aliment Pharmacol Ther. 2002;16:
1333 – 9.
15) Bai JC, Fried M, Corazza GR, et al. World Gastroenterology Organisation global
guidelines on celiac disease. J Clin Gastroenterol 2013;47:121–126.
16) Advances in diagnosis and management of celiac disease. Kelly CP, Bai JC, Liu
E, Leffler DA. Gastroenterology. 2015 May;148(6):1175-86.
Revision Date: 3/24/16
Author: Author: Javier A. Villafuerte Gálvez, MD, Abhijeet Yadav, MD
Editors: Melinda Dennis, MS, RD, LDN and Daniel Leffler MD
