Preferred Initial Serologic Blood Test for Celiac Disease
The preferred initial serologic blood test for a patient suspected of celiac disease who is on a gluten-containing diet is IgA tissue transglutaminase (tTG-IgA) combined with total IgA level. 1
Primary Testing Strategy
IgA tTG should be ordered alongside total IgA level to identify IgA deficiency, which occurs in 1-3% of celiac disease patients and causes falsely negative IgA-based antibody tests. 1, 2
IgA tTG demonstrates excellent diagnostic accuracy with 90.7% sensitivity and 87.4% specificity in adults at the 15 U/mL threshold, and 97.7% sensitivity with 70.2% specificity in children at the 20 U/mL threshold. 1, 2
This single test combination (IgA tTG + total IgA) provides the most efficient initial screening approach according to current NICE guidelines. 1
Confirmatory Testing Algorithm
If IgA tTG is positive, confirm with IgA endomysial antibody (EMA) testing, which has superior specificity of 99.6% in adults and 93.8% in children. 1, 2
When IgA tTG exceeds 10 times the upper limit of normal combined with positive IgA EMA in a second blood sample, the positive predictive value for celiac disease is virtually 100%. 1, 3
This two-step approach (tTG first, then EMA) achieves 85.7% sensitivity, 98.6% specificity, 71.7% positive predictive value, and 99.7% negative predictive value. 4
Testing in IgA-Deficient Patients
If total IgA is low or absent, order IgG-based tests including IgG deamidated gliadin peptide (DGP-IgG), which demonstrates superior diagnostic accuracy with 93.6% sensitivity and 99.4% specificity in adults. 1, 2
IgG endomysial antibody or IgG tTG can also be used in IgA-deficient patients, though IgG DGP is preferred. 1, 2
IgG tTG testing is not specific in the absence of IgA deficiency and should not be used as a primary test when IgA levels are normal. 1
Tests to Avoid in Initial Screening
Non-deamidated IgA/IgG gliadin antibodies confer no additional diagnostic benefit for detecting adult celiac disease and should not be included in initial testing. 4
IgG isotype testing for tTG antibody is not specific in the absence of IgA deficiency and should be reserved only for IgA-deficient patients. 1
Critical Prerequisites for Accurate Testing
Patients must consume at least 10g of gluten daily for 6-8 weeks prior to serological testing to avoid false-negative results. 1, 2, 3
Reduction or avoidance of gluten prior to diagnostic testing is strongly discouraged as it significantly reduces the sensitivity of both serology and biopsy testing. 1
If patients have already started a gluten-free diet, they should resume a normal diet with three slices of wheat bread daily for 1-3 months before repeat determination of tTG-IgA. 1
Common Pitfalls to Avoid
Never diagnose celiac disease based on serology alone without biopsy confirmation in adults—biopsy remains essential except in patients with coagulation disorders or pregnancy. 1, 3
Do not confuse elevated total IgA with celiac disease risk; elevated total IgA actually strengthens confidence in negative tTG IgA results by confirming the test validity. 2
Always measure total IgA levels alongside IgA-based antibody tests, as selective IgA deficiency occurs 10-15 times more frequently in celiac patients. 5