High‐titre circulating tissue transglutaminase‐2 antibodies predict small bowel villous atrophy, but decision cut‐off limits must be locally validated

Summary Numerous studies suggest that high levels of circulating immunoglobulin ( Ig)A tissue transglutaminase ( TTG 2) antibodies predict coeliac disease with high specificity. Accordingly, it has been suggested that duodenal biopsy may not be required routinely for diagnostic confirmation where quantitative serology identifies the presence of high antibody titres. However, defining a cut‐off TTG 2 threshold is problematic, as the multiple available assay methods are not harmonized and most studies have been focused on the paediatric population. Recent paediatric guidelines proposed a TTG 2 antibody diagnostic cut‐off at 10 × the upper limit of normal ( ULN ) for the method; however, concerns remain about errors of generalization, between both methods and laboratories. In this study, we used retrospective laboratory data to investigate the relationship between TTG 2 antibody levels and Marsh 3 histology in the seropositive population of adults and children at a single centre. Among 202 seropositive patients with corresponding biopsies, it was possible to define a TTG 2 antibody cut‐off with 100% specificity for M arsh 3 histology, at just over 10 ×  ULN for the method. However, UK N ational E xternal Q uality A ssurance S cheme returns during the study period showed a wide dispersion of results and poor consensus, both between methods and between laboratories using the same method. Our results support the view that high‐titre TTG 2 antibody levels have strong predictive value for villous atrophy in adults and children, but suggest that decision cut‐offs to guide biopsy requirement will require local validation. TTG 2 antibody assay harmonization is a priority, in order to meet the evolving requirements of laboratory users in this field.