From the Guidelines
If you have a negative Tissue Transglutaminase (TTG) test but elevated Immunoglobulin A (IgA) levels, celiac disease is unlikely but not completely ruled out, and you should consult with a gastroenterologist for further evaluation. The specialist may recommend additional testing such as endomysial antibody (EMA) testing, deamidated gliadin peptide (DGP) antibodies, or possibly an upper endoscopy with duodenal biopsies if clinical suspicion remains high 1. It is essential to continue your normal diet containing gluten until all testing is complete, as eliminating gluten prematurely can affect test results. Elevated IgA without positive TTG could indicate other conditions like IgA nephropathy, certain infections, liver diseases, or autoimmune disorders.
Some key points to consider in the evaluation of celiac disease include:
- The presence of TG2Ab in the serum and duodenal histological alterations usually make the diagnosis straightforward 1
- The disease is highly correlated with the presence of HLA-DQ2 and/or HLA-DQ8 molecules, and nearly 100% of individuals diagnosed with celiac disease exhibit this specific genetic profile 1
- Serologic tests are essential for an accurate diagnosis of celiac disease, and patients with suspected celiac disease but negative results from serologic tests should have their total IgA level measured 1
- A systematic review with meta-analysis found that serological tests for celiac disease are highly sensitive and specific in both adults and children 1
In terms of next steps, it is crucial to work with a gastroenterologist to determine the best course of action, as they can help interpret test results and provide guidance on further evaluation and potential treatment options. The specialist may also consider the patient's clinical symptoms, family history, and other factors in the overall assessment. Ultimately, a comprehensive evaluation is necessary to determine the cause of elevated IgA levels and to rule out or confirm celiac disease.
From the Research
Understanding Celiac Disease Diagnosis
- Celiac disease is typically diagnosed using a combination of serologic tests, including tissue transglutaminase (TTG) immunoglobulin A (IgA) antibodies, and duodenal histology 2.
- A negative TTG result but elevated IgA levels may indicate a need for further testing, as IgA deficiency can lead to false-negative results 3, 2.
Interpreting Test Results
- Elevated IgA levels in the absence of positive TTG results may suggest other conditions or the need for additional testing, such as measuring total IgA or testing for other antibodies 3.
- The utility of isolated positive tTG IgG results in diagnosing celiac disease is low, at around 3% 3.
- Tests for serum tTG IgA and EMA IgA levels have low sensitivity (below 50%) in detecting persistent villous atrophy in patients with celiac disease on a gluten-free diet 4.
Next Steps
- If the probability of celiac disease is high, despite a negative TTG result, consider measuring total IgA or testing for other antibodies, such as endomysial antibodies (EMA) 3, 2.
- A small bowel biopsy may be necessary to confirm the diagnosis, especially in cases with elevated IgA levels and negative TTG results 3, 5.
- Monitoring and follow-up testing, including repeat TTG-IgA examinations, are crucial in managing celiac disease and detecting potential complications 5, 2.