I have a weakly positive deamidated gliadin peptide (DGP) antibody test—what does this indicate and what are the appropriate next steps to evaluate for celiac disease?

Weakly Positive Deamidated Gliadin Antibody: Interpretation and Next Steps

A weakly positive deamidated gliadin peptide (DGP) antibody test has limited diagnostic value and requires confirmation with tissue transglutaminase IgA (tTG-IgA) testing plus total IgA measurement before proceeding to duodenal biopsy. 1

Understanding the Test Result

• DGP antibodies show lower sensitivity and specificity compared to tTG-IgA, with DGP-IgA demonstrating a tendency toward lower sensitivity (84.3%) versus tTG-IgA (93.7%) in prospective studies. 2
• The positive predictive value of isolated DGP positivity is only 15.5% when tTG-IgA is negative, meaning most weakly positive DGP results do not represent celiac disease. 3
• DGP testing performs similarly to tTG-IgA for monitoring dietary adherence in established celiac disease but is not the preferred initial screening test. 1

Immediate Next Steps

1. Order Confirmatory Serology

• Measure tTG-IgA plus total IgA level immediately to determine if this represents true celiac disease or a false-positive result. 1, 4
• Total IgA measurement is essential because IgA deficiency (present in 1–3% of celiac patients) causes falsely negative IgA-based tests and would require IgG-based testing instead. 1, 5
• If tTG-IgA is also elevated, proceed to endomysial antibody (EMA) testing for confirmation, which has excellent specificity (99.6% in adults). 1, 4

2. Verify Adequate Gluten Intake

• Confirm the patient consumed at least 10g of gluten daily for 6–8 weeks before testing, as insufficient gluten exposure is the leading cause of false-negative results. 1, 4
• If the patient has already reduced gluten intake, the weakly positive DGP may represent early dietary changes rather than active disease. 1
• Patients must resume regular gluten consumption (equivalent to 3 slices of wheat bread daily) for 1–3 months before repeat testing if gluten intake was inadequate. 4

Interpretation Based on Confirmatory Testing

If tTG-IgA is Positive (≥15 U/mL in adults)

• Proceed directly to upper endoscopy with at least 6 duodenal biopsies from the second part of the duodenum or beyond, as this combination has high positive predictive value. 1, 4
• The combination of positive tTG-IgA and positive DGP increases diagnostic confidence, though biopsy remains mandatory in adults. 2, 6
• When tTG-IgA exceeds 10× the upper limit of normal AND EMA is positive on repeat sample, the positive predictive value approaches 100%. 4

If tTG-IgA is Negative

• The isolated weakly positive DGP has only 15.5% positive predictive value for celiac disease, making it an unreliable standalone marker. 3
• Consider alternative explanations: other autoimmune conditions, inflammatory bowel disease, chronic infections, or false-positive result. 4
• Do not proceed to biopsy based solely on isolated DGP positivity unless clinical suspicion remains extremely high (e.g., first-degree relative with celiac disease, type 1 diabetes, unexplained iron deficiency). 1, 3

If IgA Deficiency is Detected

• Switch to IgG-based testing immediately: IgG deamidated gliadin peptide (DGP-IgG) is the preferred test, with superior accuracy (93.6% sensitivity, 99.4% specificity). 4, 2
• IgG DGP identified 2 of 3 celiac patients with IgA deficiency who were negative on all IgA-based tests in prospective studies. 2
• IgG tTG has limited utility (sensitivity only 40.6–84.6%) and should not be used as the primary IgG test. 4

Clinical Context Matters

High Pre-Test Probability Scenarios (Proceed to Biopsy Even with Weak Serology)

• First-degree relatives of celiac patients (7.5% prevalence). 1
• Type 1 diabetes (5–10% prevalence of celiac disease). 1
• Autoimmune thyroid disease, autoimmune liver disease. 1
• Unexplained iron deficiency anemia (celiac present in 2–6%). 4
• Down syndrome or Turner syndrome. 1

Low Pre-Test Probability (Do Not Pursue Further Testing)

• Non-specific gastrointestinal symptoms without risk factors. 1
• Population prevalence is only 1%, making false-positives more likely than true disease. 1

Common Pitfalls to Avoid

• Never start a gluten-free diet before completing the diagnostic workup, as this invalidates both serology and biopsy results. 1, 4, 5
• Do not rely on DGP testing alone without tTG-IgA confirmation, as DGP has inferior diagnostic accuracy. 1, 2, 3
• Do not order multiple antibody panels simultaneously in low-risk individuals, as this reduces specificity without meaningful sensitivity gains. 4
• Elderly patients (>70 years) have higher rates of seronegative celiac disease (50% negative tTG-IgA, 36% negative DGP), so maintain lower threshold for biopsy in this population. 7

Special Populations

Children Under 2 Years

• Combining tTG-IgA with DGP-IgG and DGP-IgA improves sensitivity in young children. 5
• Pediatric thresholds differ: tTG-IgA has 97.7% sensitivity at 20 U/mL cutoff. 5

Patients Already on Gluten-Free Diet

• HLA-DQ2/DQ8 testing has >99% negative predictive value—absence of both alleles essentially excludes celiac disease. 1, 4
• Reserve HLA testing for equivocal cases or when patients cannot resume gluten intake. 1

Algorithm Summary

1. Measure tTG-IgA + total IgA immediately. 1, 4
2. If tTG-IgA positive: Add EMA for confirmation → Proceed to endoscopy with ≥6 biopsies. 1, 4
3. If tTG-IgA negative + normal IgA: Isolated DGP positivity has low predictive value—consider alternative diagnoses unless high-risk population. 3
4. If IgA deficient: Repeat with IgG DGP (preferred) or IgG tTG → Proceed to biopsy if positive. 4, 2
5. If all serology negative but high clinical suspicion: Verify adequate gluten intake → Consider HLA testing or proceed directly to biopsy. 1, 7