From the Guidelines
To diagnose celiac disease, I recommend ordering serologic testing, including tissue transglutaminase antibodies (tTG-IgA) and total serum IgA, as the initial tests, as supported by the most recent and highest quality study 1.
Key Laboratory Tests
- Serologic testing for tTG-IgA, which is the most sensitive and specific initial test
- Total serum IgA to rule out IgA deficiency, which occurs in about 2-3% of celiac patients and can cause false negative results
- Deamidated gliadin peptide antibodies (DGP-IgG) or tTG-IgG if IgA deficiency is present
- Endomysial antibodies (EMA-IgA) can be used as a confirmatory test due to its high specificity
Additional Recommendations
- These tests should be performed while the patient is on a gluten-containing diet, as elimination of gluten can lead to false negative results, as emphasized in 1 and 1
- After positive serologic testing, patients should undergo an upper endoscopy with multiple duodenal biopsies for histological confirmation, which remains the gold standard for diagnosis, as stated in 1 and 1
- Genetic testing for HLA-DQ2 and HLA-DQ8 haplotypes can be helpful in certain situations, particularly to rule out celiac disease in ambiguous cases, as nearly all celiac patients carry at least one of these genetic markers, as noted in 1 and 1
- Complete blood count and comprehensive metabolic panel should also be ordered to assess for anemia, liver function abnormalities, and nutritional deficiencies commonly seen in celiac disease, as suggested in the example answers
Important Considerations
- The patient's diet should be carefully reviewed to ensure they are on a gluten-containing diet prior to testing, as recommended in 1
- A thorough medication history should be collected to identify potential etiologies of villous atrophy, as advised in 1
From the Research
Laboratory Tests for Diagnosing Celiac Disease
The following laboratory tests are recommended for diagnosing celiac disease (CD):
- Anti-tissue transglutaminase antibody (tTG) test 2, 3, 4
- Endomysial antibody (EmA) test 2, 3, 4
- Deamidated gliadin peptide (DGP) antibody test 2, 5, 3
- Anti-gliadin antibody (AGA) test 4
Characteristics of Laboratory Tests
The characteristics of these laboratory tests are as follows:
- Sensitivity and specificity of IgA and IgG DGP antibodies: 85.7% and 92.2% for IgA, 92.9% and 100% for IgG 2
- Sensitivity and specificity of tTG antibodies: 93.7% and 96.6% for IgA tTG 3
- Sensitivity and specificity of EmA antibodies: 91.6% and 100% for IgA EmA 3
- Positive and negative predictive values of IgG DGP antibodies: 100% and 96.2% 2
Clinical Utility of Laboratory Tests
The clinical utility of these laboratory tests is as follows:
- The combined search for IgA tTG and IgG DGP antibodies provides the best diagnostic accuracy for CD 3
- DGP antibody testing can identify cases of CD in tTG-negative individuals, although the low positive predictive value suggests that the yield may be low 5
- Tests for serum tTG IgA and EmA IgA levels have low sensitivity (below 50%) in detection of persistent villous atrophy in patients with CD on a gluten-free diet 6