What does a positive Celiac Antibody (AB) tissue transglutaminase (tTG) Immunoglobulin A (IgA) result indicate in a patient with reflux?

Celiac Antibody tTG IgA Testing in Patients with Reflux

A positive tissue transglutaminase (tTG) IgA antibody test indicates a high probability of celiac disease and requires confirmatory upper endoscopy with small bowel biopsy, regardless of whether the patient presents with reflux symptoms. 1

What the Test Result Means

Positive tTG IgA has excellent diagnostic accuracy for celiac disease:

• Sensitivity of 90.7% and specificity of 87.4% in adults at the commonly used threshold of 15 U/mL 2
• Sensitivity of 97.7% and specificity of 70.2% in children at the threshold of 20 U/mL 2
• The test performs better at ruling out celiac disease than ruling it in, due to the specificity being lower than sensitivity 2

The magnitude of elevation matters clinically:

• tTG IgA levels >10× the upper limit of normal strongly correlate with severe intestinal villous atrophy and have a positive predictive value approaching 100% 1, 3
• Levels ≥7× the cutoff identify all patients with significant mucosal damage (Marsh ≥2) with 100% specificity and positive predictive value 3

Critical Next Steps

You must complete the following diagnostic workup before initiating treatment:

1. Measure total IgA level to rule out IgA deficiency, which occurs in 1-3% of celiac disease patients and causes falsely low tTG IgA results 1

2. Consider endomysial antibody (EMA) testing as a confirmatory test, which has higher specificity (99.6% in adults, 93.8% in children) and may help rule in celiac disease 2, 1

3. Refer for upper endoscopy with small bowel biopsy - this remains the gold standard for diagnosis. Obtain at least 6 specimens from the second part of the duodenum or beyond 1

4. Screen for associated conditions:

   • Iron deficiency anemia (CBC and iron studies) - celiac disease is present in 2-6% of patients with unexplained iron deficiency 1
   • Autoimmune thyroid disease (thyroid function tests) 1
   • Type 1 diabetes (fasting glucose or HbA1c) 1

Relationship to Reflux Symptoms

Reflux can be a presenting symptom of celiac disease, though it is not the most common manifestation. Patients with celiac disease typically present with:

• Gastrointestinal symptoms: diarrhea, abdominal pain, bloating, weight loss 1
• Extra-intestinal manifestations: fatigue, irritability, inability to concentrate 1
• Reflux symptoms may improve with treatment of underlying celiac disease

Critical Pitfalls to Avoid

Never start a gluten-free diet before completing the diagnostic workup - this leads to false negative serology and inconclusive biopsies, making definitive diagnosis impossible 1

Do not rely solely on serology without biopsy confirmation - even with high tTG IgA levels, biopsy is needed to confirm diagnosis and assess degree of intestinal damage, especially when results are discordant 1

Ensure the patient is consuming gluten at the time of testing - serologic testing must be performed while on a gluten-containing diet to avoid false negative results 1, 4

If IgA Deficiency is Found

If total IgA is low or absent, repeat testing using IgG-based assays:

• IgG deamidated gliadin peptide (DGP) 1
• IgG tTG 1
• These have sensitivity of 93.6% and specificity of 99.4% for IgG DGP in adults 2

Post-Diagnosis Management

Once celiac disease is confirmed by biopsy:

• Initiate strict gluten-free diet immediately after biopsy confirmation 1
• Refer to a registered dietitian experienced in celiac disease management 1, 4
• Monitor tTG IgA levels at 6 months, 12 months, then annually to assess dietary compliance 1
• Persistently elevated tTG IgA despite treatment indicates ongoing gluten exposure or poor dietary compliance 1, 4

Different tTG IgA assays have varying sensitivity for detecting suboptimal treatment response - some chemiluminescence assays are more sensitive than fluorochrome-enzyme assays in detecting ongoing intestinal damage during follow-up 5