What are the diagnostic tests for celiac disease (CD)?

From the Guidelines

The diagnosis of celiac disease should begin with blood tests to detect specific antibodies, including tissue transglutaminase antibodies (tTG-IgA) and endomysial antibodies (EMA), while the patient is on a gluten-containing diet, as recommended by the most recent guidelines 1. The diagnosis of celiac disease is a complex process that involves serological testing and intestinal biopsy.

Key Steps in Diagnosis

• Blood tests to detect specific antibodies, including tTG-IgA and EMA, should be performed while the patient is on a gluten-containing diet, as eliminating gluten before testing can lead to false-negative results.
• If blood tests are positive or if there's a strong clinical suspicion despite negative blood tests, an upper endoscopy with small intestinal biopsies is necessary for confirmation.
• During this procedure, multiple biopsy samples are taken from the duodenum to look for characteristic changes such as villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.
• Genetic testing for HLA-DQ2 and HLA-DQ8 can be helpful in certain situations, particularly to rule out celiac disease in ambiguous cases, as almost all celiac patients carry at least one of these genetic markers.

Important Considerations

• For accurate diagnosis, patients should continue consuming gluten (equivalent to at least 4 slices of bread daily) for 6-8 weeks before testing, as recommended by recent guidelines 1.
• In children with very high antibody levels, intestinal biopsy may sometimes be avoided according to recent guidelines, but this approach is less common in adults.
• The most recent and highest quality study on the topic, published in 2022, provides a robust and up-to-date evaluation of the accuracy of serological tests for celiac disease in adults and children 1.

Diagnostic Approach

• The diagnostic approach to celiac disease has undergone important changes in recent years, with serologic tests becoming a relatively sensitive and specific way to initially detect the disease 1.
• The IgA antiendomysial antibody (EMA) and the IgA tTGA are the preferred serologic tests for detecting celiac disease, with the IgA tTGA being both sensitive and specific for the disease 1.
• In cases of selective IgA deficiency, IgG-based testing with IgG tTG and IgG DGP, and IgG EMA can be used to diagnose celiac disease 1.

From the Research

Diagnostic Tests for Celiac Disease

• The diagnosis of celiac disease can be made using various tests, including serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) 2, 3, 4.
• These tests are commonly used to screen for celiac disease in patients consuming gluten, but they can also be used to monitor patients on a gluten-free diet (GFD) 2.
• The sensitivity and specificity of tTG IgA and EMA IgA assays in identifying patients with celiac disease who have persistent villous atrophy despite a GFD have been evaluated in a meta-analysis 2.
• The results showed that the serum assays identified patients with persistent villous atrophy with high levels of specificity, but with low levels of sensitivity: 0.50 for the tTG IgA assay and 0.45 for the EMA IgA assay 2.

Antibodies for Celiac Disease Diagnosis

• Immunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG-ab) have been reported to correlate closely with IgA antiendomysial antibodies (EMA) and can be used as a diagnostic marker for celiac disease 3.
• The sensitivity, specificity, and predictive value of tTG-ab measured by a commercially available ELISA technique have been compared with those of EMA and IgA antigliadin antibodies (AGA) for the diagnosis of celiac disease 3.
• The results showed that tTG-ab had a sensitivity of 100%, specificity of 94%, positive predictive value of 93%, and negative predictive value of 100% for the diagnosis of celiac disease 3.

Progress in Serology-Based Diagnosis

• Current serological tests in celiac disease have some of the best performance characteristics among disease-specific tests, but there is still a need for more accurate non-invasive markers of mucosal damage in children and adults with celiac disease who are following a GFD 5.
• A 'biopsy avoidance strategy' has been implemented in pediatric celiac disease, and it is envisaged that the next 5 years will see an increasing reliance on serology in the diagnosis of adult celiac disease 5.
• The progression of celiac disease in children with antibodies against tissue transglutaminase and normal duodenal architecture has been investigated, and the results showed that the cumulative incidence of progression to villous atrophy was 43% over a 12-year period 6.

Commercial Kits for Celiac Disease Diagnosis

• A commercial kit for quantitative determination of antibody in patients with untreated celiac disease has been assessed, and the results showed that the kit was highly sensitive and specific for detection of celiac disease 4.
• However, there was an incomplete overlapping with antiendomysial antibody, and a very high variability of values between laboratories was detected when absolute values were considered 4.