Interpretation of tTG IgA Level of 3 U/mL with Normal Total IgA
A tissue transglutaminase IgA level of 3 U/mL is negative and effectively rules out celiac disease when the total IgA is normal at 363 mg/dL, requiring no further celiac-specific testing. 1
Diagnostic Accuracy of This Result
The negative tTG IgA result has a negative predictive value approaching 100% when the patient has been consuming adequate gluten, making it highly reliable for excluding celiac disease. 1
The normal total IgA level of 363 mg/dL confirms that IgA-based antibody tests are valid and not falsely negative due to IgA deficiency, which occurs in 1-3% of celiac patients and would invalidate the tTG IgA result. 2, 1
In adults, tTG IgA demonstrates 90.7% sensitivity and 87.4% specificity at standard diagnostic thresholds (typically 15 U/mL), meaning a value of 3 U/mL is well below any diagnostic threshold. 1, 2
Clinical Significance
No further celiac-specific workup is needed with this combination of negative tTG IgA and normal total IgA in a patient consuming gluten. 1
The elevated total IgA level (363 mg/dL is above normal range) actually strengthens confidence in the negative tTG IgA result, as it confirms the patient can mount an IgA response. 2
Important Caveats to Consider
The patient must have been consuming adequate gluten (at least 10g daily for 6-8 weeks) before testing to avoid false-negative results. If the patient had already reduced or eliminated gluten intake, the test may be unreliable. 1, 2
Approximately 2-10% of patients with actual celiac disease could theoretically have false-negative results, but this occurs primarily in patients who have already reduced gluten intake or have very early/mild disease. 1
When to Reconsider Testing
Repeat celiac screening may be warranted if new symptoms develop (chronic diarrhea, weight loss, malabsorption) or in high-risk populations (type 1 diabetes, first-degree relatives of celiac patients, autoimmune thyroid disease), even with previously negative serology. 1
If clinical suspicion remains very high despite negative serology, proceed to upper endoscopy with duodenal biopsies or consider HLA-DQ2/DQ8 genetic testing—absence of both alleles has >99% negative predictive value and essentially rules out celiac disease. 1
Addressing the Elevated Total IgA
The elevated total IgA (363 mg/dL) should prompt investigation for other causes including chronic infections, inflammatory bowel disease, liver disease (cirrhosis, chronic hepatitis), or autoimmune conditions. 2
Consider obtaining comprehensive metabolic panel, liver function tests, urinalysis with microscopy, and serum protein electrophoresis if clinically indicated to evaluate for IgA-related disorders such as IgA nephropathy, IgA vasculitis, or IgA monoclonal gammopathy. 2