What is the recommended initial testing for celiac disease, including serologies?

From the Guidelines

The initial testing for celiac disease should involve serological screening with tissue transglutaminase immunoglobulin A (tTG-IgA) antibody test as the first-line test, along with total serum IgA measurement to rule out IgA deficiency, as recommended by recent guidelines and supported by the systematic review with meta-analysis published in 2022 1. This approach provides high sensitivity and specificity for detecting celiac disease while accounting for potential false negatives in IgA-deficient patients. Key points to consider in the initial testing for celiac disease include:

• Measuring serum total IgA and IgA tTG as the first step for patients suspected of having celiac disease 1
• Detection of IgA EMA and/or IgA DGP might be indicated in specific cases, especially if there is a discrepancy between these antibodies
• If IgA deficiency is identified, patients should undergo serum IgG-based testing with IgG tTG and IgG DGP, and IgG EMA, as selective or partial IgA deficiency occurs more frequently in patients with celiac disease compared to healthy controls 1
• It is crucial that patients continue consuming gluten-containing foods before testing, as a gluten-free diet can lead to false-negative results; at least 6 weeks of regular gluten consumption is recommended prior to testing, as suggested by the guidelines 1 While serological tests are excellent screening tools, a definitive diagnosis typically requires an endoscopic small intestinal biopsy showing characteristic villous atrophy, which should be performed while the patient is still on a gluten-containing diet. However, recent guidelines have begun to move towards biopsy-avoidance strategies for celiac disease in children and adults, especially in cases with high tTG-IgA levels and positive IgA EMA, highlighting the importance of interpreting serological results in the context of clinical presentation and other diagnostic criteria 1.

From the Research

Celiac Serologies

The recommended initial testing for celiac disease includes serologies such as:

• Tissue transglutaminase antibodies (tTG) (IgA) 2
• Deamidated gliadin peptide (DGP) (IgA and IgG) 2, 3, 4, 5
• Endomysial antibodies (EMA) (IgA) 2, 3, 5

Diagnostic Performance

The diagnostic performance of these serologies is as follows:

• tTG (IgA): sensitivities and specificities in the range of 0.76-0.968 and 0.909-0.98, respectively 2
• DGP (IgA and IgG): sensitivities and specificities in the range of 0.69-0.984 and 0.903-1, respectively 2
• EMA (IgA): sensitivities and specificities in the range of 0.61-0.937 and 0.98-1, respectively 2
• Combination assays (DGP + tTG and DGP (IgA + IgG)): sensitivities and specificities in the range of 0.87-1 and 0.8-1, respectively 2

Clinical Utility

The clinical utility of these serologies is:

• DGP and tTG show equivalent diagnostic performance for celiac disease 2
• The combined search for IgA tTGA and IgG DGP-AGA provides the best diagnostic accuracy for celiac disease 3
• DGP antibody testing can identify cases of celiac disease in TTG-negative individuals, although the low positive predictive value suggests that the yield may be low 4
• The detection of HLA-DQ2 and HLA-DQ8 can help reinforce or exclude the diagnosis of gluten sensitivity in cases with positive serology but with mild or absent intestinal lesions 6