The HLA DQ2 and DQ8 haplotypes are two genetic variations that have long been known to be associated with an increased risk of celiac disease. Most people who develop celiac disease carry either the DQ2 haplotype or the DQ8 haplotype. A recent study has now identified a genotype which may actually protect an individual from developing celiac disease and decrease their lifetime risk of developing the disease. The Environmental Determinants of Diabetes in the Young (TEDDY) study is a large ongoing multicenter study, primarily set up for the analysis of type 1 diabetes. This study has also provided an enormous amount of data on the HLA genes that are linked to an increased risk of celiac disease. Before the symptoms of celiac disease are apparent, there is typically a development of tissue transglutaminase autoantibodies (tTGAs). These autoantibodies are not routinely screened for in typical early childhood tests, but have been analyzed in participants of the TEDDY study at two years of age. Children who tested positive for tTGAs in consecutive samples (taken 3-6 months apart) were classified as having celiac disease autoimmunity (CDA), a very early stage of celiac disease which can precede the clinical diagnosis by several months or even years. All participants in the TEDDY study have HLA types that put them at increased risk of diabetes and celiac disease (i.e. one or more copies of the DQ2 and DQ8 haplotypes). From this large group (8,676 infants), research led by Hadley et al. (Am J Gastroenterol, June 2015) discovered that children who carried an HLA allele known as DPB1*04:01 had a 29% reduction in risk of CDA compared to the children that lacked this allele. This study demonstrates that while there are certain well known HLA alleles which can greatly increase an individual’s lifetime risk of developing celiac disease, there are also certain types of HLA alleles which are protective against celiac disease and may decrease risk. This will lead to future advancements in genetic testing panels for celiac disease which can potentially identify not only the HLA alleles which increase a person’s lifetime risk of developing celiac disease but also inform individuals whether they are carry the protective HLA alleles and are at decreased risk. As more genetic variations are identified that are linked to celiac disease risk, genetic testing will be able to paint an increasingly comprehensive picture of an individual’s risk of suffering from this common but serious autoimmune disorder. References: Hadley D et al. (2015). HLA-DPB1*04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study. Am J Gastroenterol. 110(6): 915-920.