BACKGROUND AND AIMS:Intestinal inflammation in inflammatory bowel diseases (IBD) is thought to be T cell mediated and therefore dependent on the interaction between the T-cell receptor (TCR) and human leukocyte antigen (HLA) proteins expressed on antigen presenting cells.The collection of all TCRs in one individual, known as the TCR repertoire, is characterized by enormous diversity and inter-individual variability. It was shown that healthy monozygotic (MZ) twins are more similar in their TCR repertoire than unrelated individuals. Therefore, MZ twins concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire that could potentially be used as disease biomarkers.METHODS AND RESULTS:Employing unique molecular barcoding that can distinguish between PCR artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of which were discordant and 4 concordant for IBD. We observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared to their healthy twins.CONCLUSIONS:Our findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterize inflammatory bowel diseases and to identify potential biomarkers and true disease causes.