ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-OR48

A Regimen of Nonmyeloablative Conditioning and CD8+/TCR- Facilitating Cells Tips the Balance Towards Immune Downregulation and Away From Cytopathic Activity in Kidney Allograft Recipients

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Lee, John Richard, Weill Cornell Medicine, New York, New York, United States
  • Leventhal, Joseph, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Li, Carol Y., Weill Cornell Medicine, New York, New York, United States
  • Ildstad, Suzanne, Talaris Therapeutics, Inc., Louisville, Kentucky, United States
  • Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
Background

We tested the hypothesis that tolerance induced with a regimen of nonmyeloablative conditioning and CD8+/TCR- facilitating cells (FCR001) is associated with immune down regulation and away from cytopathic activity.

Methods

Blinded to clinical status and biopsy diagnosis, the Laboratory quantified urinary cell mRNA levels in 28 urines from 14 FCR001-tolerant patients with durable chimerism and off immunosuppression per protocol(FCR DC off IS); 23 urines from 12 FCR001-tolerant patients with DC and on immunosuppression per protocol(FCR DC on IS); 43 biopsy-matched urines from 34 kidney allograft recipients from the Clinical Trials in Organ Transplantation-04(CTOT-04) study and TCMR biopsies (TCMR Cohort); and 161 biopsy-matched urines from 124 recipients from CTOT-04 study with No Rejection biopsies (NR Cohort).

Results

In accord with negative immune regulation in tolerant patients, urinary cell mRNA levels of CTLA-4 were significantly higher in the FCR DC off or on IS than the TCMR cohort or the NR Cohort (P <0.05, Wilcoxon rank sum test, Table 1). In accord with lack of cytopathic activity in tolerant patients, levels of Granzyme B and Perforin were significantly lower or no different in the FCR DC off or on IS compared to the NR cohort (Table 1). Levels of additional mRNAs in the FCR DC on or off IS were significantly lower than the TCMR Cohort and mostly similar to that in the NR Cohort (Table 1).

Conclusion

Tolerance induced with a nonmyeloablative conditioning regimen and CD8+/TCR- facilitating cells is characterized by tipping of the balance towards immune down regulation and away from cytopathic activity.

Table 1
GeneFCR Durable off IS Median CopiesFCR Durable on IS Median CopiesNo Rejection Group Median CopiesTCMR Group Median CopiesFCR Durable off IS vs. No Rejection P ValueFCR Durable off IS vs. TCMR P valueFCR Durable on IS vs. No Rejection P valueFCR Durable on IS vs. TCMR P valueTCMR vs. No Rejection P Value
CTLA4439575131356 x 10^-150.0054 x 10^-144 x10^-42 x 10^-12
CD31239178236088260.065 x 10^-50.0020.0067 x 10^-11
Granzyme B10620733733040.0083 x10^-90.474 x10^-68 x10^-10
Perforin9227722341190.252 x 10^-80.481 x 10^-59 x 10^-11
IP101532667514450.171 x 10^-50.030.0021 x 10^-10
FoxP3131313730.330.0070.200.032 x 10^-5
TGFb1218230454589151420.011 x 10^-70.682 x 10^-41 x 10^-5
18S rRNA4 x 10^86 x 10^87 x 10^82 x 10^90.081 x10 ^-50.410.0036 x 10^-5
CTLA4/Granzyme B Ratio5.621.360.040.037 x 10^-156 x10^-163 x10^-123 x10^-100.61