Clinical Information

Clinical Indications

This assay is intended to support the evaluation of individuals with suspected celiac disease, including:

• Patients presenting with gastrointestinal symptoms suggestive of malabsorption
• Individuals with non-classic or extraintestinal manifestations potentially related to gluten sensitivity
• Persons at increased risk due to family history or associated autoimmune/genetic conditions
• Evaluation of dermatitis herpetiformis (in conjunction with endomysial antibody testing)
• Monitoring adherence to and response following initiation of a gluten-free diet

Clinical Background

Celiac disease is a chronic immune-mediated condition triggered by exposure to gluten in genetically predisposed individuals. Ingestion of gluten-containing grains leads to immune activation directed against tissue transglutaminase within the small intestinal mucosa, resulting in varying degrees of villous injury.

Although many patients experience gastrointestinal complaints such as diarrhea, abdominal discomfort, or weight loss, clinical presentation is highly variable. Some individuals demonstrate primarily extraintestinal findings, including iron deficiency anemia, low bone density, delayed growth, reproductive complications, oral ulcers, neurologic symptoms, chronic fatigue, or dermatitis herpetiformis. Celiac disease is more common in individuals with autoimmune thyroid disease, type 1 diabetes mellitus, Down syndrome, and selective IgA deficiency.

Genetic predisposition is strongly linked to the presence of HLA-DQ2 and/or HLA-DQ8 haplotypes. These markers are present in the majority of affected individuals but are also common in the general population; therefore, their presence indicates susceptibility rather than confirming disease. HLA testing may be useful in selected cases, particularly when serologic and histologic findings are discordant or when testing occurs after gluten restriction has begun.

Definitive diagnosis is based on histologic findings from duodenal biopsy. However, serologic assays are widely used to determine which patients warrant biopsy. Among available markers, tTG IgA demonstrates the highest sensitivity and specificity in individuals with normal IgA production. In patients with IgA deficiency, IgG-based testing (tTG IgG and/or deamidated gliadin IgG) is recommended.

The American College of Gastroenterology suggests that, in selected pediatric cases, markedly elevated tTG IgA levels (e.g., greater than 10 times the upper limit of normal) combined with a positive endomysial antibody result in a separate sample may allow diagnosis without biopsy, at the discretion of the treating physician.

Treatment consists of lifelong adherence to a gluten-free diet. With dietary compliance, antibody concentrations typically decline over time and may normalize. Persistent elevation may reflect continued gluten exposure or refractory disease.

For accurate diagnostic interpretation, testing should be performed while the patient is consuming gluten.

Reference Intervals

Tissue Transglutaminase Antibody, IgA

• <4.0 U/mL: Negative
• 4.0–10.0 U/mL: Borderline/Weakly positive
• >10.0 U/mL: Positive

Tissue Transglutaminase Antibody, IgG

• <6.0 U/mL: Negative
• 6.0–9.0 U/mL: Borderline/Weakly positive
• >9.0 U/mL: Positive

Reference intervals apply to all age groups unless otherwise specified.

Result Interpretation

• Detection of tTG IgA and/or IgG antibodies supports an immune response consistent with celiac disease and may also be observed in dermatitis herpetiformis.
• Antibody concentrations below the assay cutoff reduce the likelihood of celiac disease but do not completely exclude the diagnosis in all circumstances.
• Following initiation of a gluten-free diet, declining antibody levels may indicate therapeutic response.

Limitations and Important Considerations

• This assay is intended as a diagnostic aid and should not be used as the sole basis for diagnosis or exclusion of disease.
• Testing performed after gluten restriction has begun may yield falsely low or negative results.
• In patients with negative tTG IgA and positive tTG IgG, selective IgA deficiency should be considered and total IgA measurement may be helpful.
• Negative serologic findings do not completely rule out celiac disease. If significant clinical suspicion persists, particularly in patients with overt malabsorption, further evaluation with endoscopy and biopsy should be considered.
• Results must be interpreted in conjunction with clinical presentation and, when appropriate, additional serologic markers such as endomysial antibodies or deamidated gliadin antibodies.
• A negative result in IgA-based testing may occur in individuals with IgA deficiency and does not exclude disease.
• Performance characteristics have been established for serum specimens only.