TY  - JOUR
A1  - Ritter, Julia
A1  - Zimmermann, Karin
A1  - Jöhrens, Korinna
A1  - Mende, Stefanie
A1  - Seegebarth, Anke
A1  - Siegmund, Britta
A1  - Hennig, Steffen
A1  - Todorova, Kremena
A1  - Rosenwald, Andreas
A1  - Daum, Severin
A1  - Hummel, Michael
A1  - Schumann, Michael
T1  - T-cell repertoires in refractory coeliac disease
JF  - Gut
N2  - Objective Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. Design DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n= 8), RCD type II (n= 8) and unclassified Marsh I cases (n= 3) collected from 2002 to 2013 was examined by TCR beta-complementarity- determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. Results On average, 106 sequence reads per sample were generated consisting of up to 900 individual TCR beta rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6% of all TCR beta rearrangements, which was significantly higher than in controls (6.8%; p<0.01) or RCD type I (6.7%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliad-independent CDR3 motifs were only detectable at low frequencies. Conclusions TCR beta-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCR beta rearrangements. Dominant TCR beta sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.
KW  - Intestinal Intraepithelial Lymphocy
KW  - Delta Repertoire
KW  - Lymphoma
KW  - Usage
KW  - Clonality
KW  - Sprue
KW  - Chains
KW  - Design
KW  - Epitope
KW  - Frequency
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226350
VL  - 67
IS  - 4
ER  - 
TY  - JOUR
A1  - Biedermann, Benedikt
A1  - Bräuer, Stephan
A1  - Denner, Ansgar
A1  - Pellen, Mathieu
A1  - Schumann, Steffen
A1  - Thompson, Jennifer M.
T1  - Automation of NLO QCD and EW corrections with SHERPA and RECOLA
JF  - European Physical Journal C
N2  - This publication presents the combination of the one-loop matrix-element generator Recola with the multipurpose Monte Carlo program Sherpa. Since both programs are highly automated, the resulting Sherpa +Recola framework allows for the computation of – in principle – any Standard Model process at both NLO QCD and EW accuracy. To illustrate this, three representative LHC processes have been computed at NLO QCD and EW: vector-boson production in association with jets, off-shell Z-boson pair production, and the production of a top-quark pair in association with a Higgs boson. In addition to fixed-order computations, when considering QCD corrections, all functionalities of Sherpa, i.e. particle decays, QCD parton showers, hadronisation, underlying events, etc. can be used in combination with Recola. This is demonstrated by the merging and matching of one-loop QCD matrix elements for Drell–Yan production in association with jets to the parton shower. The implementation is fully automatised, thus making it a perfect tool for both experimentalists and theorists who want to use state-of-the-art predictions at NLO accuracy.
KW  - RECOLA
KW  - SHERPA
KW  - NLO QCD
KW  - EW
KW  - Higgs boson
KW  - Large Hadron Collider
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170615
VL  - 77
IS  - 492
ER  -