Frontiers in Immunology (Nov 2022)

Perturbations of the T-cell immune repertoire in kidney transplant rejection

  • Tara K. Sigdel,
  • Paul A. Fields,
  • Juliane Liberto,
  • Izabella Damm,
  • Maggie Kerwin,
  • Jill Hood,
  • Parhom Towfighi,
  • Marina Sirota,
  • Harlan S. Robins,
  • Minnie M. Sarwal

DOI
https://doi.org/10.3389/fimmu.2022.1012042
Journal volume & issue
Vol. 13

Abstract

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In this cross-sectional and longitudinal analysis of mapping the T-cell repertoire in kidney transplant recipients, we have investigated and validated T-cell clonality, immune repertoire chronology at rejection, and contemporaneous allograft biopsy quantitative tissue injury, to better understand the pathobiology of acute T-cell fraction, T-cell repertoire and antibody-mediated kidney transplant rejection. To follow the dynamic evolution of T-cell repertoire changes before and after engraftment and during biopsy-confirmed acute rejection, we sequenced 323 peripheral blood samples from 200 unique kidney transplant recipients, with (n=100) and without (n=100) biopsy-confirmed acute rejection. We report that patients who develop acute allograft rejection, have lower (p=0.01) T-cell fraction even before transplantation, followed by its rise after transplantation and at the time of acute rejection accompanied by high TCR repertoire turnover (p=0.004). Acute rejection episodes occurring after the first 6 months post-transplantation, and those with a component of antibody-mediated rejection, had the highest turnover; p=0.0016) of their T-cell repertoire. In conclusion, we validated that detecting repertoire changes in kidney transplantation correlates with post-transplant rejection episodes suggesting that T-cell receptor sequencing may provide recipient pre-transplant and post-transplant predictors of rejection risk.

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