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C.S. Link-Rachner et al.
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Figure 6. Graft-versus-host disease (GvHD) and T-cell receptor alpha (TRα) diversity. (A) Simpson’s diversity index (Ds) on day 60 (left) and day 180 (right) of the naïve and memory TRA repertoire of each patient following transplantation. Repertoire diversity is mapped in relation to the occurrence of acute GvHD (aGvHD). Left: patients suffering from aGvHD prior to or at the first time of sampling (day 60 following transplantation) were designated "early". Patients with aGvHD past the first next-generation sequencing (NGS) sampling were designated "late". (B) Simpson’s diversity index (Ds) on day 60 (left) and day 180 (right) following transplan- tation of the naïve and memory TRA repertoire of each patient. Repertoire diversity is mapped in relation to the occurrence of chronic GvHD (cGvHD).
has previously shown that these patients have a unique repertoire in the first month following transplantation but become donor-like during the first year post transplanta- tion.13 Given the small number of patients in our study, and our focus on the first six months following transplan- tation, no significant changes towards a more donor-like repertoire were observed in any of the patients in the observed time. However, a donor-like memory repertoire was evident in 2 patients, with more than 90% of the memory repertoire represented by clonotypes that were also identified in the donor's repertoire.
It is still not known whether certain changes in the TCR repertoire render patients more prone to immunological complications post transplantation, such as acute and chronic GvHD as well as viral infections. Published stud- ies addressing the relation between TCR diversity and GvHD are controversial. One of the first studies to ana- lyze the TRb repertoire in transplanted patients found that patients with aGvHD (≥Grade II) had a higher TRb diver- sity.9 In contrast, other studies have shown the association of aGvHD and/or cGvHD with a more clonal TRb reper-
authors assumed that the naïve-derived TCR repertoire established in the first month following SCT does not per- sist longer, and memory-derived clonotypes dominate the long-lasting TCR repertoire.13
In our study, when comparing the TRα repertoires of donors and recipients, we observed that a high percentage of shared reads in both the naïve (approx. 50% of reads) and memory (approx. 80%) repertoires was derived from the memory compartment of the donor, but only approxi- mately 10% of reads were derived from the naïve compart- ment. These results indicate that, in the absence of T-cell depletion, a large proportion of the donor's memory reper- toire contributes to the initial TRα reconstitution in trans- planted patients. Of note, the 2 patients (TCR_011 and TCR_040) with new highly dominant clonotypes in their memory repertoires that were not detected in the donor repertoires were diagnosed with extensive cGvHD during the observation period. It remains to be clarified in further studies whether there is an association between extensive GvHD and the appearance of newly dominant clonotypes.
T-cell receptor-α sequencing in patients receiving PTCy
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haematologica | 2019; 104(3)