First-Line Test for Celiac Disease
IgA tissue transglutaminase antibody (tTG-IgA) is the recommended first-line test for celiac disease, and must be performed alongside total IgA level measurement to rule out IgA deficiency. 1, 2
Initial Serologic Testing Strategy
tTG-IgA serves as the preferred single screening test with sensitivity of 90-96% and specificity >95% in adults, making it the most efficient initial diagnostic tool 1, 2, 3
Total IgA level must be measured concurrently because selective IgA deficiency occurs in 1-3% of celiac patients and causes falsely negative IgA-based antibody tests 1, 2
Testing must be performed while the patient is consuming adequate gluten (at least 10g daily for 6-8 weeks prior to testing) to avoid false-negative results 1, 2, 4
Special Considerations for This Patient
Given the 22-year-old asymptomatic patient with BMI of 17:
The low BMI warrants testing despite absence of symptoms, as celiac disease frequently presents with minimal or atypical manifestations including unexplained weight loss or failure to maintain normal weight 1, 5
Asymptomatic presentation does not reduce test accuracy when proper serologic testing is performed, though it may slightly affect the positive predictive value compared to symptomatic patients 1
If IgA Deficiency is Detected
Switch to IgG-based testing immediately if total IgA is low or absent 1, 2
IgG deamidated gliadin peptide (DGP-IgG) is the preferred IgG test with superior diagnostic accuracy (93.6% sensitivity, 99.4% specificity) compared to tTG-IgG 6, 2
Do not use IgG tTG in patients with normal IgA levels, as it has poor specificity (78-89%) and limited sensitivity (40.6-84.6%) in this setting 1, 6
Confirmatory Testing Algorithm
If tTG-IgA is positive, obtain IgA endomysial antibody (EMA) as confirmatory testing with excellent specificity of 99.6% 1, 6, 2
When tTG-IgA exceeds 10× the upper limit of normal combined with positive EMA in a second blood sample, the positive predictive value approaches 100% 1, 4
Proceed to upper endoscopy with at least 6 duodenal biopsies (1-2 from bulb, 4+ from second portion of duodenum or beyond) to confirm diagnosis before initiating gluten-free diet 1, 2, 4
Critical Pitfalls to Avoid
Never initiate a gluten-free diet before completing diagnostic workup, as this leads to false-negative serology and inconclusive biopsies 1, 2, 4
Do not rely on IgG-based tests as first-line screening in patients with normal IgA levels, as they have markedly inferior accuracy 6, 2
Avoid point-of-care tests for initial diagnosis due to quality control concerns and lack of standardization, despite their convenience 1
Do not diagnose celiac disease based on serology alone without biopsy confirmation in adults, as intestinal biopsy remains the gold standard 2, 4, 3