PMID- 31711184 OWN - NLM STAT- MEDLINE DCOM- 20210517 LR - 20210517 IS - 1876-4479 (Electronic) IS - 1873-9946 (Print) IS - 1873-9946 (Linking) VI - 14 IP - 6 DP - 2020 Jul 9 TI - Identification of Disease-associated Traits and Clonotypes in the T Cell Receptor Repertoire of Monozygotic Twins Affected by Inflammatory Bowel Diseases. PG - 778-790 LID - 10.1093/ecco-jcc/jjz179 [doi] AB - 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 characterised 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 which could potentially be used as disease biomarkers. METHODS: Employing unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRalpha and TCRbeta repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD. RESULTS: 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 with 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 characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes. CI - (c) European Crohn's and Colitis Organisation (ECCO) 2019. FAU - Rosati, Elisa AU - Rosati E AD - Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany. FAU - Pogorelyy, Mikhail V AU - Pogorelyy MV AD - Laboratory of comparative and functional genomic, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation. AD - Department of Translational Medicine, Pirogov Russian National Research Medical University [RNRMU], Moscow, Russian Federation. FAU - Dowds, C Marie AU - Dowds CM AD - Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany. FAU - Moller, Frederik T AU - Moller FT AD - Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. FAU - Sorensen, Signe B AU - Sorensen SB AD - Focused Research Unit for Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Denmark. AD - Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. FAU - Lebedev, Yuri B AU - Lebedev YB AD - Laboratory of comparative and functional genomic, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation. FAU - Frey, Norbert AU - Frey N AD - Department of Internal Medicine III, University Hospital Schleswig-Holstein, Kiel, Germany. FAU - Schreiber, Stefan AU - Schreiber S AD - Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. FAU - Spehlmann, Martina E AU - Spehlmann ME AD - Department of Internal Medicine III, University Hospital Schleswig-Holstein, Kiel, Germany. FAU - Andersen, Vibeke AU - Andersen V AD - Focused Research Unit for Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Denmark. AD - Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. AD - IRS-Center Sonderjylland, University of Southern Denmark, Odense, Denmark. FAU - Mamedov, Ilgar Z AU - Mamedov IZ AD - Laboratory of comparative and functional genomic, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation. AD - Department of Translational Medicine, Pirogov Russian National Research Medical University [RNRMU], Moscow, Russian Federation. AD - Laboratory of molecular biology, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation. AD - CEITEC, Masaryk University, Brno, Czech Republic. FAU - Franke, Andre AU - Franke A AD - Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany. LA - eng PT - Journal Article PT - Twin Study PL - England TA - J Crohns Colitis JT - Journal of Crohn's & colitis JID - 101318676 RN - 0 (Leukocyte L1 Antigen Complex) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) RN - 9007-41-4 (C-Reactive Protein) SB - IM EIN - J Crohns Colitis. 2020 Jun 19;14(5):720. PMID: 31968069 MH - Adult MH - C-Reactive Protein/analysis MH - *Colitis, Ulcerative/diagnosis/immunology/physiopathology MH - *Crohn Disease/diagnosis/immunology/physiopathology MH - Denmark MH - Feces MH - Female MH - *Genes, T-Cell Receptor alpha MH - *Genes, T-Cell Receptor beta MH - Germany MH - Humans MH - Leukocyte L1 Antigen Complex/analysis MH - Male MH - Patient Acuity MH - Receptors, Antigen, T-Cell, alpha-beta/*blood MH - Sequence Analysis, DNA MH - Smoking/immunology MH - Twins, Monozygotic PMC - PMC7346890 OTO - NOTNLM OT - T cell receptor [TCR] repertoire OT - inflammatory bowel diseases [IBD] OT - monozygotic twins EDAT- 2019/11/12 06:00 MHDA- 2021/05/18 06:00 PMCR- 2019/10/11 CRDT- 2019/11/12 06:00 PHST- 2019/11/12 06:00 [pubmed] PHST- 2021/05/18 06:00 [medline] PHST- 2019/11/12 06:00 [entrez] PHST- 2019/10/11 00:00 [pmc-release] AID - 5621358 [pii] AID - jjz179 [pii] AID - 10.1093/ecco-jcc/jjz179 [doi] PST - ppublish SO - J Crohns Colitis. 2020 Jul 9;14(6):778-790. doi: 10.1093/ecco-jcc/jjz179.