The frequency of HLA-DQ7 in patients at risk of coeliac disease: A haplotype to be reckoned with for screening?

HLA-DQ2 and -DQ8 carriers are genetically predisposed to develop coeliac disease (CD). Testing negative for HLA-DQ2/DQ8 has a high negative predictive value. Full HLA-DQ genotyping as well as tests only typing for HLA-DQ2/DQ8 are therefore used for screening at-risk populations. However, HLA-DQ7 positive and HLA-DQ2/DQ8 negative CD patients have been described in various populations. In this study we examine the relevance for HLA-DQ7 typing in a large at-risk CD population. The HLA-DQ status of all paediatric and adult patients at-risk of CD that were typed in a tertiary medical centre laboratory between 2012 and 2016 (n = 3983) was obtained. HLA-DQ7 (HLA-DQB1*03:01) positive and HLA-DQ2/DQ8 negative patients were selected. We gathered information on serology, histology and dietary status, and CD diagnosis. In total, 489/3983 patients were HLA-DQ7-positive and HLA-DQ2/DQ8 negative, and after exclusion (missing data on diet or serology/histology), 325 were included. Only one adult patient was diagnosed with CD, based on a duodenal biopsy and a clinical response to a gluten-free diet. Homozygosity was observed in 14.8 %. Based on the current cohort additional typing of HLA-DQ7 does not seem relevant for screening at-risk populations for CD in the Netherlands. It should be considered in patients with a high suspicion of CD.