Diagnostic Evaluation of Seronegative Celiac Disease

Celiac disease (CeD) is an autoimmune condition that is traditionally characterized by the presence of serologic markers and flattening of the duodenal villi. However, a rare variant of the disease known as seronegative celiac disease (SNCeD), is characterized by an absence of these diagnostic serologies. The current diagnostic approach to this condition relies on excluding alternative seronegative enteropathies and confirming a positive CeD HLA genotype followed by an extended gluten-free diet (GFD). However, this current diagnostic approach is burdensome and underscores the need for more succinct methods. Encouragingly there are multiple tests that are being investigated for CeD diagnosis that also could extend to SNCeD diagnosis such as intestinal IgA anti-TG2 deposits, HLA-DQ tetramer assays, microRNA, interleukin-2, and flow cytometry among others.