From the Guidelines
To diagnose celiac disease, the initial laboratory tests should include serological testing with tissue transglutaminase antibody (tTG-IgA) and total serum IgA, as well as IgA against deamidated gliadin peptide, and endomysial antibody (IgA) as recommended by the most recent guidelines 1. The tTG-IgA test is highly sensitive and specific for celiac disease, while the total IgA measurement helps identify IgA deficiency, which could lead to false-negative results. If IgA deficiency is present, deamidated gliadin peptide antibodies (DGP-IgG) or tTG-IgG should be ordered instead, as patients with total IgA levels below the lower limit of detection and IgG against tissue transglutaminase or deamidated gliadin peptide, or endomysial antibody, should be considered to have celiac disease with selective IgA deficiency rather than seronegative celiac disease 1. These blood tests should be performed while the patient is on a gluten-containing diet, as elimination of gluten can reduce antibody levels and lead to false-negative results, as emphasized in recent clinical practice updates 1. Key points to consider when ordering laboratory tests for celiac disease include:
- Measuring serum total IgA and IgA tTG as the first step for patients suspected of having celiac disease 1
- Using IgA anti-tissue transglutaminase (TTG) antibody as the preferred test in persons older than two years, and combining TTG IgA testing with IgG- and IgA-deamidated gliadin peptides in younger children to improve sensitivity 1
- Obtaining or reviewing serum total IgA levels in patients with possible seronegative celiac disease, as selective or partial IgA deficiency occurs more frequently in patients with celiac disease compared to healthy controls 1
- Considering genetic testing for HLA-DQ2 and HLA-DQ8 in certain situations, particularly to rule out celiac disease in ambiguous cases, although a positive genetic test alone cannot diagnose celiac disease since these markers are present in about 30-40% of the general population 1.
From the Research
Laboratory Tests for Celiac Disease
To diagnose celiac disease, the following laboratory tests can be ordered:
- Immunoglobulin A (IgA) tissue transglutaminase antibody (tTG) test, which is the preferred test for screening patients for celiac disease 2
- Total serum IgA level to exclude selective IgA deficiency and avoid false-negative test results 2
- Endomysial antibody (EMA) test, which is highly sensitive and specific for celiac disease 3
- Human leukocyte antigens (HLA) DQ2 and DQ8 testing to help exclude the diagnosis of celiac disease 2
Interpretation of Test Results
When interpreting test results, it is essential to consider the following:
- A positive serologic test result should be followed by a referral to a gastroenterologist for endoscopic small intestinal biopsies to confirm the diagnosis 2
- A gluten-free diet should not be started before confirming the diagnosis of celiac disease 2
- The sensitivity and specificity of serologic tests for celiac disease can vary, with the tTG IgA and EMA IgA tests being highly sensitive and specific 3
Special Considerations
In certain populations, such as children, serological testing can be used to establish a diagnosis of celiac disease, but better international standardization of the assays is required 4 The use of serological tests for monitoring adherence to a gluten-free diet is limited, and additional research is needed to improve noninvasive tools for follow-up 4