Understanding the Diagnostic Importance and Clinical Significance of tTG and DGP Antibodies in Celiac Disease
Introduction
Celiac disease is a chronic autoimmune disorder triggered by the ingestion of gluten in genetically predisposed individuals. Early diagnosis is critical to prevent complications such as malabsorption, osteoporosis, infertility, and intestinal lymphoma. Among the tools available for diagnosis, serological testing for specific antibodies—namely, tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP)—plays a pivotal role.
This blog explores the diagnostic importance and clinical significance of tTG and DGP antibodies, helping clinicians and patients better understand their role in the diagnostic algorithm for celiac disease.
What Are tTG and DGP Antibodies?
Tissue Transglutaminase (tTG) is an enzyme that modifies gluten peptides, making them more immunogenic in people with celiac disease. The immune system mistakenly targets this enzyme, leading to the production of anti-tTG antibodies, particularly of the IgA class.
Deamidated Gliadin Peptide (DGP) antibodies, on the other hand, target gluten-derived peptides that have undergone a chemical change (deamidation) by tTG. The immune response to DGP is especially relevant in younger children and in certain patient populations who may not exhibit elevated tTG levels.
Diagnostic Importance
1. tTG-IgA: The First-Line Test
- High Sensitivity and Specificity: tTG-IgA is considered the most reliable single serological test for celiac disease, with sensitivity and specificity often exceeding 90–95%.
- Routine Screening Tool: Used as the initial test in most clinical guidelines.
- Correlates with Mucosal Damage: Elevated tTG-IgA levels often correlate with the degree of villous atrophy seen in intestinal biopsies.
2. Total IgA Measurement
- Why It Matters: Since celiac patients have a higher risk of selective IgA deficiency, measuring total serum IgA is crucial. If IgA is deficient, tTG-IgA could yield a false negative.
3. tTG-IgG and DGP-IgG: For IgA Deficiency
- In IgA-deficient patients, tTG-IgG and DGP-IgG become essential alternatives.
- DGP-IgG is particularly useful in:
- Young children under 2 years old
- Patients with atypical symptoms or early disease
- Those with borderline or negative tTG-IgA but persistent clinical suspicion
4. DGP-IgA: Complementary Role
- DGP-IgA is less commonly used alone but may complement other tests in equivocal cases.
Clinical Significance
1. Non-Invasive Diagnosis
- High titers of tTG-IgA (10x upper limit of normal), combined with positive EMA (anti-endomysial antibodies) and compatible HLA typing, can allow for a biopsy-free diagnosis in children per ESPGHAN guidelines.
2. Monitoring Adherence to a Gluten-Free Diet
- Serologic markers, especially tTG and DGP, help monitor adherence and response to a gluten-free diet (GFD). A decline in antibody levels typically indicates compliance and mucosal healing.
3. Predicting Complications
- Persistently elevated antibodies despite a GFD may indicate:
- Continued gluten exposure
- Poor compliance
- Potential refractory celiac disease
4. Differential Diagnosis
- Negative tTG and DGP tests in a patient with gastrointestinal symptoms suggest other causes like IBS, IBD, or wheat allergy, helping refine the differential diagnosis.
Summary Table: Diagnostic Utility
| Test | Sensitivity | Specificity | Ideal Use Case |
|---|---|---|---|
| tTG-IgA | High | High | First-line screening in most patients |
| tTG-IgG | Moderate | High | IgA-deficient patients |
| DGP-IgG | High | Moderate | Young children, early/atypical cases |
| DGP-IgA | Variable | Variable | Supplementary use |
| Total IgA | — | — | To assess IgA sufficiency |
Conclusion
Serological testing for celiac disease has evolved to become both accurate and accessible. tTG-IgA remains the cornerstone of diagnosis, while DGP antibodies, particularly DGP-IgG, offer valuable support in specific populations such as children or IgA-deficient individuals. Understanding the nuances of these markers allows for earlier diagnosis, better disease monitoring, and improved patient outcomes.
If you or someone you know is experiencing chronic digestive issues, fatigue, or unexplained nutrient deficiencies, consult a healthcare provider about screening for celiac disease using these critical tests.
