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Identification of Disease-associated Traits and Clonotypes in the T Cell Receptor Repertoire of Monozygotic Twins Affected by Inflammatory Bowel Diseases

E. Rosati, MV. Pogorelyy, CM. Dowds, FT. Moller, SB. Sorensen, YB. Lebedev, N. Frey, S. Schreiber, ME. Spehlmann, V. Andersen, IZ. Mamedov, A. Franke

. 2020 ; 14 (6) : 778-790. [pub] 2020Jul09

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, studie na dvojčatech

Perzistentní odkaz   https://www.medvik.cz/link/bmc21020361

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 TCRα and TCRβ 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.

Citace poskytuje Crossref.org

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$a BACKGROUND AND AIMS: Intestinal inflammation in inflammatory bowel diseases [IBD] is thought to be T cell mediated and therefore dependent on the interaction between the T cell receptor [TCR] and human leukocyte antigen [HLA] proteins expressed on antigen presenting cells. The collection of all TCRs in one individual, known as the TCR repertoire, is characterised by enormous diversity and inter-individual variability. It was shown that healthy monozygotic [MZ] twins are more similar in their TCR repertoire than unrelated individuals. Therefore MZ twins, concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire which could potentially be used as disease biomarkers. METHODS: Employing unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD. RESULTS: We observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared with their healthy twins. CONCLUSIONS: Our findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes.
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$a Pogorelyy, Mikhail V $u Laboratory of comparative and functional genomic, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation $u Department of Translational Medicine, Pirogov Russian National Research Medical University [RNRMU], Moscow, Russian Federation
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$a Dowds, C Marie $u Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
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$a Moller, Frederik T $u Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark $u Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
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$a Lebedev, Yuri B $u Laboratory of comparative and functional genomic, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
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$a Frey, Norbert $u Department of Internal Medicine III, University Hospital Schleswig-Holstein, Kiel, Germany
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$a Schreiber, Stefan $u Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany
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$a Andersen, Vibeke $u Focused Research Unit for Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Denmark $u Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark $u IRS-Center Sønderjylland, University of Southern Denmark, Odense, Denmark
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$a Mamedov, Ilgar Z $u Laboratory of comparative and functional genomic, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation $u Department of Translational Medicine, Pirogov Russian National Research Medical University [RNRMU], Moscow, Russian Federation $u Laboratory of molecular biology, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation $u CEITEC, Masaryk University, Brno, Czech Republic
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