Advances in Celiac Disease Testing: From method validation to serological diagnosis

Celiac disease (CD) serology plays an important role in CD screening, diagnosis and monitoring of dietary adherence and ongoing mucosal inflammation. Numerous societies have universally recommended CD screening in gluten-exposed individuals through serologic testing for IgA autoantibodies to tissue transglutaminase (tTG IgA), as the most sensitive screening test. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHN) has recommended a biopsy in symptomatic children with positive tTG IgA or asymptomatic at-risk children with positive tTG IgA or tTG IgG. The European Society Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) has proposed a no-biopsy option for children with tTG IgA result of ≥10 times the upper limit of normal (10XULN), if endomysial IgA antibody (EMA IgA) is positive in a second blood sample Since the analytical performance of serology assays has not been standardized, large inter-assay variability and variable concordance with confirmatory methods can be found. Therefore, assays and testing algorithms should be carefully evaluated for clinical and analytical performance by testing laboratories. In particular, the dose-response relationships amongst tTG IgA assays are often non-linear and therefore, implementation of the 10X ULN cut-off should be carefully evaluated. This presentation will provide an overview of analytical methods used for serologic evaluation of celiac disease, their strengths and limitations, as well as important analytical considerations of clinical impact when one is validating a new method.

 

Learning Objectives