Allogeneic kidney transplantation is a common transplant procedure and an optimal
form of therapy for individuals who reach end-stage renal disease, significantly improving their
quality of life, as compared to dialysis and supportive care. Nonetheless, its success relies on
10 lifelong immunosuppression (IS), which causes serious complications. Moreover, despite
immunosuppression (IS), around 8% of renal transplants will be rejected due to T cell-mediated
and/or antibody-mediated reactions towards donor-specific allo-antigens. Importantly, scarce
kidney recipients achieve an immunosuppressive drug-free tolerance, suggesting the existence
of active tolerance mechanisms. Biomarkers to predict rejection risks and identify patients in
15 which tolerance mechanisms could allow IS weaning, as well as a non-invasive biomarker to
diagnose a rejection event, are highly needed to improve patient’s care. The inventors identify
circulating CD73+ DP8/ Tregs or the expansion of CD73+ DP8/ Tregs after transplantation as
a non-invasive biomarker to predict rejection risks from 3 months post-transplantation. These
data advocate for the potential value of these cells to improve kidney grafted patients/’ care
20 through IS minimization and/or tolerance-inducing therapies. Strikingly, these results were
observed in two independent cohorts, at 1-year post-transplantation.
The present invention relates to a method of determining in a subject whether a subject has or
is at a risk of developing transplant rejection comprising the steps of: i) determining the
frequency of CD73-expressing DP8α Tregs among any T cell subset in particular among total
CD3+ T cells or among total CD4+ T cells or among total CD8+
25 T cells in a sample obtained
from the subject after transplantation, ii) comparing the frequencies determined at step i) with
a predetermined reference value wherein detecting differential between the frequency of CD73-
expressing DP8α Tregs among any T cell subset in particular among total CD3+ T cells or
among total CD4+ T cells or among total CD8+ T cells determined at step i) and the
30 predetermined reference value is indicative of whether a subject has or is at a risk of developing
a transplant rejection