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

From the Guidelines

Laboratory testing for celiac disease should begin with serological tests, specifically the tissue transglutaminase (tTG) IgA antibody test, while the patient is on a gluten-containing diet, as recommended by the most recent guidelines 1. The most sensitive and specific initial test is the tTG IgA antibody test, often combined with total serum IgA to rule out IgA deficiency.

• If IgA deficiency is present, tTG IgG or deamidated gliadin peptide (DGP) IgG antibodies should be measured instead.
• Endomysial antibody (EMA) IgA testing can be used as a confirmatory test due to its high specificity. For definitive diagnosis, an intestinal biopsy showing villous atrophy is typically required, though in some cases with very high antibody titers (>10x upper limit of normal), diagnosis may be made without biopsy, particularly in children. Genetic testing for HLA-DQ2 and HLA-DQ8 haplotypes can be useful to exclude celiac disease when negative, as nearly all celiac patients carry at least one of these markers, as supported by previous studies 2, 3, 4. Laboratory monitoring after diagnosis should include follow-up antibody testing to confirm response to a gluten-free diet, typically 6-12 months after starting treatment, along with assessment for nutritional deficiencies such as iron, folate, vitamin B12, vitamin D, and zinc. Key points to consider in the diagnosis of celiac disease include:
• The importance of testing while the patient is on a gluten-containing diet
• The use of serological tests, such as tTG IgA and EMA IgA, as the initial diagnostic step
• The role of intestinal biopsy in confirming the diagnosis
• The value of genetic testing for HLA-DQ2 and HLA-DQ8 haplotypes in excluding celiac disease
• The need for ongoing laboratory monitoring after diagnosis to assess response to treatment and identify potential nutritional deficiencies.

From the Research

Celiac Disease Laboratory Tests

• Celiac disease is a chronic immune-mediated gastrointestinal condition that can be diagnosed using laboratory tests, including serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) 5.
• 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) 5.
• However, studies have shown that these tests have low sensitivity in detecting persistent villous atrophy in patients with celiac disease on a GFD, with sensitivity levels of 0.50 for the tTG IgA assay and 0.45 for the EMA IgA assay 5.

Serological Testing for Celiac Disease

• Serological tests, including IgA tissue transglutaminase antibodies (TTG-IgA), are widely used for diagnosing celiac disease and have an accuracy comparable to duodenal biopsy 6.
• However, these tests can have variable sensitivity and specificity, and there is a need for better international standardization of the assays 7.
• New biomarkers, such as anti-neo-epitope tTg check (IgG + IgA), have become available and offer high sensitivity and specificity for diagnosing celiac disease 8.

Diagnostic Criteria and Laboratory Testing

• Diagnostic algorithms for celiac disease often rely on TTG-IgA as a starting point, and human leukocyte antigen typing may also be used to determine genetic risk 6.
• Guidelines for children endorse biopsy avoidance if high levels of TTG-IgA are present, with diagnostic accuracy comparable to duodenal biopsy 6.
• A high tissue-transglutaminase antibody level can predict small intestinal villous atrophy in adult patients at high risk of celiac disease, and a cut-off value of 5 times the upper limit of normal can be used to avoid biopsy in some patients 9.