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T-cell receptors following SCT
toire.11,13 In our study, we were unable to show statistical significance for any correlation between aGvHD or cGvHD and TRα diversity. However, despite the limited number of patients and the large deviation between indi- vidual samples, there was a tendency towards higher memory diversity in patients with aGvHD on day 60 and lower TRα memory diversity in patients with cGvHD at both time points. Evidence is emerging that the associa- tion between diversity and GvHD may be individualized in each patient: single clones that expand massively can induce aGvHD, while in other cases, hundreds of clono- types may be required to achieve a similar effect.12 Another potential explanation for the lack of correlation may be that, in this study, NGS sampling was performed on day 60 and day 180 but not specifically at the time of GvHD diagnosis. Previous publications have shown that diversity is significantly lower when the sample is drawn at the time of GvHD diagnosis.11
on CMV reactivation/infection, samples were not taken close to the day of detected CMV reactivation. Nevertheless, we observed a tendency towards lower diversity in patients transplanted from a CMV-seroposi- tive donor. Lower diversity has previously been shown in patients with CMV-seropositive donors.13
Similarly, no difference in TRα diversity was observed in association with CMV reactivation. CMV reactivation induces a skewed and less diverse repertoire, as shown in one of our previous publications10 and by other groups.9,13,27 Again, since this study did not primarily focus
Funding
This work was supported by the DFG Research Center and Cluster of Excellence - Center for Regenerative Therapies Dresden (FZ 111) and the BMBF (STRATOS consortium, FKZ 01GU1108A).
Acknowledgments
The authors acknowledge Maria Schmiedgen, Denise Kühn, Christiane Gläser and Ines Partzsch for their technical assistance.
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In conclusion, this study is the first to analyze TRα repertoire reconstitution in transplanted patients focusing on different transplant regimens. Repertoire sequencing by NGS represents a new method for in-depth immune monitoring. Further studies are needed to clarify the effects and prognostic value of repertoire changes in vari- ous clinical settings.
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