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Kidney Week

Abstract: FR-OR46

Modified Immune Cell Infusion in Kidney Transplantation

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Morath, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Schaier, Matthias, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Ibrahim, Eman Hosny, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Wang, Lei, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Kleist, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Opelz, Gerhard, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Süsal, Caner, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Aly, Mostafa Gaafar, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Speer, Claudius, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Kälble, Florian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Nusshag, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Pego silva, Luiza, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Sommerer, Claudia, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Hückelhoven-Krauss, Angela, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Mehrabi, Arianeb, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Mueller-Tidow, Carsten, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States
  • Zeier, Martin G., Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Schmitt, Michael, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Terness, Peter, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Schmitt, Anita, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Daniel, Volker, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
Background

We have shown that donor blood cells, modified in vitro by an alkylating agent (MIC, modified immune cells), induced specific immunosuppression against the allogeneic donor when administered prior to transplantation. An additional finding was an up to 68-fold increase in the frequency of immunosuppressive CD19+CD24hiCD38hi transitional B lymphocytes compared to transplanted controls without MIC infusions. The question arises whether donor-specific immunosuppression and increased regulatory B lymphocytes (Breg) are permanently detectable in MIC-treated patients.

Methods

Four patients from a phase-I trial who had received 1.5x108 MIC per kg b.w. on day -7 before living donor kidney transplantation and who were on low immunosuppression were compared to 12 transplanted control patients without MIC infusions.

Results

MIC-treated patients showed an excellent clinical course with no donor-specific HLA antibodies or rejection. On day 1080 after transplantation, median serum creatinine was 1.59 mg/dL. Patients had absent in vitro lymphocyte reactivity against stimulatory donor blood cells while reactivity against third party cells was preserved as an indication of continued donor-specific unresponsiveness. CD19+CD24hiCD38hi and IL10+CD19+CD24hiCD38hi Breg were with 2.2/µL and 1.0/µL, respectively, strikingly higher than the 0.0/µL (P<0.001) and 0.0/µL (P<0.001) in transplanted controls and in the range of the numbers of healthy individuals (N=34, P=0.73 and P=0.60). In addition, significantly higher Breg numbers were found for CD1d+ (P=0.0071), CD19+CD38+CD147+CD1d+ (P=0.0071), CD19+CD25+ (P=0.0077), CD19+CD25+CD73+CD71+ (P=0.013), CD19+CD25+CD73-CD71+ (P=0.0011), CD19+CD24hiCD27+ memory (P=0.029), and IL10+CD19+CD24hiCD27+ memory Breg (P=0.042). No such differences were observed for CD4+CD25+CD127-FoxP3+ Treg (P=0.68) or different Treg subsets when comparing the four MIC-treated patients to transplanted controls without MIC infusions.

Conclusion

Donor-specific immunosuppression after MIC infusion is long-lasting and is associated with a striking increase in Breg at various stages of B cell development, including memory Breg.

Funding

  • Commercial Support