Serology Rubric • Celiac Diagnostic Matrix
Select the assay results from the pathology report to visualize the clinical interpretation profile.
Guidelines & Evidence
Verified
Last Review: 2026-07-17
When to Use
When to Use
Initial screening for Celiac Disease in symptomatic patients (diarrhea, malabsorption, bloating)
Screening high-risk asymptomatic individuals (First-degree relatives, Type 1 Diabetes, Down Syndrome)
Evaluation of "unexplained" symptoms: Iron-deficiency anemia, bone loss, or infertility
To trigger the diagnostic pathway for intestinal biopsy
Dietary Requirement
Serological testing is ONLY accurate while the patient is consuming a gluten-containing diet. False-negative results are common if the patient has already started a gluten-free diet (GFD). A "Gluten Challenge" (3-10g/day for 2-6 weeks) may be needed before testing.
How it Works
The Key Serological Markers
01
tTG-IgA (Tissue Transglutaminase): The single best screening test. High sensitivity (>95%) and specificity.
02
Total Serum IgA: Essential to exclude selective IgA deficiency (found in 1:40 Celiac patients), which can cause false-negative tTG-IgA.
03
EMA (Endomysial Antibody): Exceptionally high specificity (>99%) but operator-dependent. Often used as a confirmatory "tie-breaker."
04
DGP (Deamidated Gliadin Peptide) IgG: Useful when Total IgA is low or in children < 2 years old where tTG-IgA may be less sensitive.
Diagnostic Pathway
| Positive tTG-IgA (> 1x ULN) | Refer for Duodenal Biopsy |
| Negative tTG + Normal Total IgA | Celiac unlikely; consider HLA-DQ2/8 if clinical suspicion remains high |
| Negative tTG + Low Total IgA | Perform tTG-IgG or DGP-IgG |
Clinical Pearls
The "Biopsy-Free" Pathway (ACG 2023)
The 2023 ACG guidelines joined ESPGHAN in supporting non-biopsy diagnosis in select symptomatic adults and children who have tTG-IgA levels > 10x the Upper Limit of Normal (ULN), confirmed by a positive EMA in a separate blood draw.
HLA-DQ2 and HLA-DQ8 Testing
Celiac disease is almost impossible in the absence of HLA-DQ2 or HLA-DQ8. The "Negative Predictive Value" of HLA testing is > 99%. Use this test primarily to "rule out" Celiac when serology or biopsy is equivocal.
Clinical Pearls
Seronegative Celiac disease exists (approx. 5% of cases) — if clinical symptoms and malabsorption are severe, proceed to biopsy regardless of serology
Dermatitis Herpetiformis is pathognomonic; skin biopsy (not blood test) confirms the diagnosis
tTG levels correlate with the degree of villous atrophy (Marsh IIIa-c)
Next Steps
Management Pathway
01
Confirmed Diagnosis: Lifelong Gluten-Free Diet (GFD). Baseline DEXA scan; screen for iron/vit-D/B12 deficiency.
02
Equivocal Result: Gluten challenge followed by repeat serology or HLA testing.
The Evidence
2023 ACG Guideline
American College of Gastroenterology Clinical Guideline: Diagnosis and Management of Celiac Disease.
Rubio-Tapia A et al. • American Journal of Gastroenterology. 2023;118(1):59-76. The latest US definitive consensus.
View Source• . ;
ESPGHAN Non-Biopsy Study
European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines for diagnosing coeliac disease 2020.
Husby S et al. • J Pediatr Gastroenterol Nutr.. 2020;70(1):141-156. Establishing the 10x ULN non-biopsy rule.
View SourceOrigins & History
The Discovery of tTG
The identification of tissue transglutaminase (tTG) as the target of endomysial antibodies in 1997 revolutionized the field. Before this, diagnosis relied on less specific gliadin antibodies or mandatory multiple biopsy protocols (the "Meeuwisse" criteria).
Last Comprehensive Review: 2026-07-17