SMART-Approach Closing the genetic gap in Celiac disease

Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. It requires genetic variants in the HLA-DQA1/DQB1 locus (e.g. DQ2.5, DQ8), exposure to gluten, and additional factors like viruses to trigger the inflammatory process. Diagnosis combines symptoms (diarrhea, malabsorption, extraintestinal, like dermatitis herpetiformis), elevated tTG IgA, and biopsy showing villous atrophy/ intraepithelial lymphocytosis. Management: lifelong gluten-free diet, vitamin deficiency monitoring, which can be quite burdensome. Genetic testing offers current and future insights. First, genetic testing of the HLA region can exclude CeD (>99% NPV if HLA-DQ2/8 negative), support diagnosis in equivocal cases or identify relatives of a CeD patient at risk for CeD. Second, over 40 non-HLA genetic loci have been identified that may predict severity and guide use of immunomodulators, but gaps in our understanding and application to clinical medicine of this genomic information remain. This article highlights the author’s approach to CeD in clinical practice including use of genetic testing in some cases