Celiac Disease

Last Literature Review: November 2023 Last Update:

Celiac disease (CD), or gluten-sensitive enteropathy, is a nonallergic, immune-mediated sensitivity to gluten that can manifest in genetically susceptible individuals. Initial testing for CD typically includes assessment of both total immunoglobulin A (IgA) and tissue transglutaminase (TTG) IgA titers.    Duodenal biopsy remains the gold standard for diagnostic confirmation of CD, although specific serologic evidence may be used in lieu of biopsy to diagnose pediatric patients or to issue a diagnosis of “likely CD” in adults if biopsy is not desired or feasible.    Human leukocyte antigen (HLA) testing for CD-permissible genotypes may be useful to rule out or support a diagnosis of CD. CD risk varies among ethnicities and geographic regions, which suggests that environmental and/or lifestyle risk factors may play a role in disease etiology. 

Quick Answers for Clinicians

Who should be tested for celiac disease?

Testing for celiac disease (CD) is recommended in children, adolescents, and adults with signs, symptoms, or laboratory evidence suggestive of celiac disease (eg, malabsorption). Individuals considered at risk for CD (eg, those with a first-degree family member diagnosed with CD) should also be tested.   Refer to Indications for Testing for additional details.

Which tests should be used in the initial evaluation for celiac disease?

When celiac disease (CD) is suspected, guidelines recommend use of both a tissue transglutaminase (TTG) immunoglobulin A (IgA) test and a total serum IgA test (if selective IgA deficiency has not previously been ruled out).    If selective IgA deficiency is present, serologies should focus on CD-specific IgG antibodies. To ensure an accurate diagnosis, serologic testing must be performed while the patient is consuming a regular, gluten-containing diet.   

Biopsy may represent a diagnostic entry point for CD if small intestinal villous atrophy is discovered while investigating other etiologies. When this is the case, IgA serologies are recommended to support a diagnosis of CD. 

When should deamidated gliadin peptide testing be used to assess for celiac disease?

In general, deamidated gliadin peptide (DGP) testing is not suitable to initially assess for celiac disease (CD), although it may be used to follow up on certain serologic results. In individuals with very low immunoglobulin A (IgA) concentrations (ie, selective IgA deficiency), DGP IgG testing and/or tissue transglutaminase (TTG) IgG testing is recommended to inform additional diagnostic steps.  

In IgA-competent patients, the utility of DGP IgA testing is unresolved and current guidelines do not suggest its use, including in IgA-competent children younger than 2 years, for whom DGP testing was previously advised. Instead, guidelines recommend TTG IgA testing in all IgA-competent individuals.   In the event of weak- or moderate-positive TTG IgA results, DGP IgA or endomysial antibody (EMA) IgA testing may be considered before biopsy to increase diagnostic confidence.

What is the role of human leukocyte antigen testing in celiac disease evaluation?

Human leukocyte antigen (HLA) testing is primarily useful to exclude a diagnosis of celiac disease (CD), as the absence of a CD-permissible genotype essentially rules out the disease. Because CD-permissible genotypes are common in the general population, a positive HLA test result holds very low positive predictive value for the disease.  

HLA testing may be helpful when CD has not been definitively excluded by previous testing (eg, when seronegative CD or false seronegativity is suspected).    It can also be used to support a clinical diagnosis.

Indications for Testing

Testing for CD is recommended in children, adolescents, and adults with signs, symptoms, or laboratory evidence suggestive of CD. This includes symptomatic malabsorption, unintended weight loss, delayed puberty, abnormal liver test results, peripheral neuropathy, poor growth, and unexplained, chronic gastroenterologic symptoms.  

Testing should also be considered in individuals with risk factors for CD. This includes those with a family history of CD (in a first-degree relative), selective IgA deficiency, another autoimmune disease (eg, type 1 diabetes, autoimmune thyroiditis, autoimmune liver disease), or a condition strongly associated with CD (eg, Down syndrome, Turner syndrome).   

Criteria for Diagnosis

Diagnostic criteria for CD differ in adult and pediatric patients. Notably, guidelines support a nonbiopsy approach to confirm CD in pediatric patients, whereas biopsy is required to confirm CD in adults.   In all patients, testing should be performed while the patient is consuming a regular, gluten-containing diet.   

Pediatric Criteria for DiagnosisAdult Criteria for Diagnosis

Confirmed CD

Positive TTG IgAa result and biopsyb results consistent with CD


High-positive TTG IgAc values (>10 x ULN) and positive EMA IgAc result in a separate specimen, and symptoms consistent with CD

Confirmed CD

Positive TTG IgAa result and biopsyb results consistent with CD


Likely CD

High-positive TTG IgAc values (>10 x ULN), positive EMA IgAc result in a separate specimen, and symptoms consistent with CD

aIgG serologies (eg, TTG IgG or DGP IgG) should be used in those with selective IgA deficiency.

bFor duodenal biopsy, collect at least five specimens: one or more specimens from the bulb and four or more specimens from the second and third parts of the duodenum.   Intestinal damage is assessed using the modified Marsh classification of histologic findings in CD  or the simplified Corazza system classification. 

cIgG serologies cannot be used to meet this diagnostic criterion.

DGP, deamidated gliadin peptide; EMA, endomysial antibody; ULN, upper limit of normal

Sources: Rubio-Tapia, 2023 ; Husby, 2020 ; Husby, 2019 ; Oberhuber, 1999 ; Corazza, 2007 

Laboratory Testing


Serology and duodenal biopsy play a central role in diagnosing CD. When CD is suspected based on clinical presentation, serology should be used to screen for biomarkers specific to CD (eg, TTG). Positive serologic results are typically confirmed by biopsy.  Negative serologic results can be followed with a biopsy to rule out possible seronegative CD when the pretest suspicion for CD is high.   In some patients, incidental biopsy findings while investigating other etiologies may be the diagnostic entry point for CD. In such cases, IgA serologies are recommended to support a diagnosis.  

Serology and biopsy must be performed while the patient is consuming a regular, gluten-containing diet to ensure accurate test results.    In individuals already adhering to a gluten-free diet, HLA testing may be useful to rule out CD or support the need for further testing following a gluten challenge (ie, reintroduction of gluten to the patient’s diet). 

IgA Serologies

Recent pediatric guidelines have proposed a nonbiopsy diagnostic approach in pediatric patients who meet strict IgA results criteria.  In adults, the same IgA results can be used to issue a diagnosis of “likely CD” when biopsy is refused or is not feasible.  In both adult and pediatric patients, including those younger than 2 years, TTG IgA and total IgA concentrations should be assessed concurrently as a first step.

In those with high-positive TTG IgA titers, defined as greater than 10 times the upper limit of normal, endomysial antibody (EMA) IgA testing can be used to confirm a CD diagnosis in children or to establish a diagnosis of likely CD in adults.  

In individuals with selective IgA deficiency (ie, undetectable total IgA concentrations), an uncommon but notable cause of false-negative IgA test results, CD-specific IgG antibodies should be tested.   

IgG Serologies

Because IgG serologies are not considered specific for CD in IgA-competent patients, they are generally not used as first-line tests. In adults and children (including those younger than 2 years) with selective IgA deficiency, TTG IgG and/or DGP IgG testing is recommended. Biopsy should be used to follow up a positive IgG result.  Notably, IgG results cannot be used to meet the diagnostic criteria for a nonbiopsy approach. 

HLA Genotyping

Associations of HLA-DQ2 and HLA-DQ8 with CD are among the strongest HLA-disease associations currently known. HLA-DQ2 and/or HLA-DQ8 is present in almost all individuals with CD.

Because these genotypes are common in the general population, a positive HLA result does not confirm a diagnosis of CD. However, it can be used to inform the need for further testing, such as in patients adhering to a gluten-free diet prior to diagnosis, or to support a diagnosis (eg, when seronegative CD is suspected ). A negative HLA result reliably rules out CD. 


In patients with confirmed CD, TTG/DGP serology and histology can be used periodically to assess therapeutic response. Other tests (eg, CBC, essential nutrients, liver enzymes) should be considered to establish a baseline prior to treatment.  

Seroconversion (ie, from positive serology at diagnosis to negative serology during treatment) is a good indicator of adherence to a gluten-free diet. Persistent-positive TTG/DGP results suggest ongoing exposure to gluten. Serology is not useful to determine mucosal healing or to detect minor dietary lapses. Biopsy is the only reliable means to determine mucosal healing, although complete healing may not occur in all patients.   

Follow-up, including repeat labs, is recommended at least twice within the first year of treatment (at intervals of 3-6 months) and at least once a year thereafter.    Biopsy is recommended after 2 years of treatment.  Repeat biopsy should be performed after a further 12 months in patients found to have treatment-resistant small intestinal damage (ie, Marsh 2-3 histologic results). 

ARUP Laboratory Tests

Additional testing is available from ARUP Laboratories; refer to the Laboratory Test Directory for a complete list of test options for CD.


Preferred Reflexive Panel Testing

For more information, refer to the Celiac Disease Reflexive Cascade, Serum Test Fact Sheet.

IgA Serologies
IgG Serologies
HLA Genotyping


Medical Experts



Julio Delgado, MD, MS
Executive Vice President, ARUP Laboratories
Professor, Vice Chairman, and Chief, Division of Clinical Pathology, University of Utah Department of Pathology