What is the screening test for celiac disease (CD)?

From the Guidelines

Screening for celiac disease should begin with serologic testing, specifically tissue transglutaminase immunoglobulin A (tTG-IgA) antibody test, which has high sensitivity (93%) and specificity (98%) 1. This approach is supported by recent guidelines and studies, which emphasize the importance of early detection and diagnosis of celiac disease to prevent long-term complications such as malnutrition, osteoporosis, and increased risk of certain cancers. The tTG-IgA test is the most sensitive and specific initial test, and it should be performed while the patient is on a gluten-containing diet, as elimination of gluten before testing can lead to false-negative results. For those with IgA deficiency, which affects about 2-3% of celiac patients, testing should include deamidated gliadin peptide antibodies (DGP IgG) or total IgA level. If serologic tests are positive, the diagnosis should be confirmed with an upper endoscopy and small intestinal biopsy, which can provide evidence of compatible small bowel damage and villous atrophy 1. Screening is recommended for first-degree relatives of celiac patients, individuals with type 1 diabetes, autoimmune thyroid disease, Down syndrome, Turner syndrome, or those with unexplained symptoms like chronic diarrhea, weight loss, iron-deficiency anemia, or elevated liver enzymes. A systematic review with meta-analysis also supports the use of serological tests for diagnosing coeliac disease, highlighting their high sensitivity and specificity in both adults and children 1. However, it is essential to note that the diagnosis of celiac disease should be based on a combination of serological tests and intestinal biopsy, as serological tests alone may not be sufficient to confirm the diagnosis. In cases where the diagnosis is uncertain, HLA typing can be useful in ruling out the condition when the results are negative 1. Overall, early detection and diagnosis of celiac disease are crucial to prevent long-term complications and improve the quality of life for affected individuals. Key points to consider when screening for celiac disease include:

• Use of tTG-IgA as the initial serologic test
• Performance of tests while the patient is on a gluten-containing diet
• Consideration of IgA deficiency and use of alternative tests such as DGP IgG or total IgA level
• Confirmation of diagnosis with upper endoscopy and small intestinal biopsy
• Screening of at-risk populations, including first-degree relatives and individuals with certain medical conditions.

From the Research

Screening for Celiac Disease

To screen for celiac disease, several tests can be used, including:

• Serum endomysial antibodies (EMA)
• Antibodies to tissue transglutaminase (tTG)
• Immunoglobulin A (IgA) tissue transglutaminase
• Antigliadin tests

Test Sensitivity and Specificity

The sensitivity and specificity of these tests vary:

• The tTG IgA assay has a sensitivity of 0.50 (95% CI, 0.41-0.60) and a specificity of 0.83 (95% CI, 0.79-0.87) 2
• The EMA IgA assay has a sensitivity of 0.45 (95% CI, 0.34-0.57) and a specificity of 0.91 (95% CI, 0.87-0.94) 2
• IgA tissue transglutaminase is the single most efficient serological test for the diagnosis of celiac disease 3
• Immunoglobulin A antibodies to tissue transglutaminase have a sensitivity of 100%, a specificity of 94%, a positive predictive value of 93%, and a negative predictive value of 100% 4

Clinical Considerations

When interpreting serological test results, it is essential to consider the full clinical scenario 3

• Serological testing can be used to identify symptomatic individuals who need a confirmatory biopsy, to screen at-risk populations, or to monitor diet compliance in patients previously diagnosed with celiac disease
• Duodenal histology has traditionally been the gold standard of diagnosis, but serological tests, especially IgA tissue transglutaminase antibodies, are widely used and diagnostic algorithms are based primarily on these tests 5
• Human leukocyte antigen typing may also be incorporated to determine genetic risk for celiac disease 5

Test Selection

The choice of test depends on the specific clinical scenario:

• Standardized ELISA-based assays for IgA autoantibodies against tissue transglutaminase remain the test of choice for most populations 6
• Antigliadin tests are no longer recommended for the diagnosis of classical celiac disease, but may be useful in the diagnosis of gluten-sensitive irritable bowel syndrome 3