Digesting all the options: Laboratory testing for celiac disease

Celiac disease is a complex immune-mediated disorder that is triggered by ingestion of gluten and related proteins in genetically susceptible individuals. Under conditions of increased intestinal permeability, gluten-derived peptides can travel across the intestinal epithelium and undergo deamidation catalyzed by the tissue transglutaminase (TTG) enzyme. This renders them immunogenic in individuals expressing specific human leukocyte antigen (HLA) DQ heterodimers. The resulting immune response is characterized by the production of antibodies against both deamidated gliadin peptides (DGP) and TTG, generation of pro-inflammatory cytokines and activation of cytotoxic T cells. This response damages the intestinal epithelium resulting in the wide range of gastrointestinal and systemic symptoms observed in those with celiac disease. Celiac disease diagnosis has traditionally been based on biopsy and histological examination of the small intestine. While this approach is still considered the gold standard, it is invasive and susceptible to both false-positive and false-negative results. Several laboratory tests have become available to aid in the diagnosis and monitoring of celiac disease, and are the focus of this review. These include serological tests for celiac disease-specific antibodies such as anti-endomysial antibodies, anti-TTG antibodies and anti-DGP antibodies of both the immunoglobulin A (IgA) and immunoglobulin G (IgG) class, genetic tests to elucidate HLA DQ status and ancillary tests such as total IgA. While some have suggested that laboratory tests may replace intestinal biopsy in specific circumstances, others maintain that this procedure remains a critical component of celiac disease diagnosis. We review the analytical methodology, strengths, weaknesses, diagnostic performance and clinical utility of the various laboratory tests for celiac disease. Potential future markers and tests that are now considered obsolete are also discussed. Current clinical practice guidelines for the diagnosis and management of celiac disease from the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, the American College of Gastroenterology and the World Gastroenterology Organisation are summarized, and important differences between these guidelines are highlighted.