Combined Serology and Genotyping Reduces False Positive Diagnosis of Celiac Disease

A new diagnostic approach for detection of celiac disease (CD) that combines genomic assessment and serology revealed that this immune disorder is far more common in the Australian population than previously thought but was often diagnosed incorrectly.

Investigators at the Walter and Eliza Hall Institute (Victoria, Australia) and their colleagues combined traditional antibody testing for CD (measuring the immune response to gluten) with an assessment of specific genetic risk markers.

They evaluated serum samples from 356 patients with biopsy-confirmed CD, and from two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. The samples were tested for antigluten antibodies by standard serological techniques and (HLA)-DQ genotyping was performed using Taqman SNP genotyping methods (Applied Biosystems, Foster City, CA, USA) following the manufacturer’s protocols.

Results revealed that celiac disease potentially affected at least one in 60 Australian women and one in 80 men. Previous estimates had suggested that the number of Australians with celiac disease was no more than 1%. Furthermore, serogenetic data indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.

“Currently, bowel biopsies are recommended for anybody with positive antibody tests,” said contributing author Dr. Jason Tye-Din, a gastroenterologist at the Walter and Eliza Hall Institute. “In this study, the inclusion of a simple genetic test helped identify a substantial number of people whose antibody tests were falsely positive and who did not actually require a bowel biopsy to test for the possibility of celiac disease.”

“It is concerning that a significant number of people in the community with celiac disease have not been diagnosed,” said Dr. Tye-Din. “Accurate and timely diagnosis is important for the health of patients with celiac disease. Making a diagnosis based on a blood test alone or commencing a gluten-free diet without a confirmatory bowel biopsy is inappropriate and can impose an unnecessary and lifelong treatment. Although small bowel biopsy is needed to confirm celiac disease, it is costly and invasive. Reducing unnecessary procedures is better for patients, eliminating an invasive test, and better for the economy by reducing healthcare costs. This study provides a strategy to improve the diagnosis of celiac disease in the community by combining the benefits of antibody and genetic testing.”

Related Links:
Applied Biosystems
Walter and Eliza Hall Institute