Kidney Week

Abstract: FR-OR46

Modified Immune Cell Infusion in Kidney Transplantation

Session Information

• In-Depth Look at Transplantation: Basic and Translational
  October 23, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Transplantation

• 1902 Transplantation: Clinical

Authors

• Morath, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Christian Morath, MD

• Schaier, Matthias, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Matthias Schaier,

• Ibrahim, Eman Hosny, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Eman Hosny Ibrahim,

• Wang, Lei, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Lei Wang,

• Kleist, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Christian Kleist,

• Opelz, Gerhard, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Gerhard Opelz,

• Süsal, Caner, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Caner Süsal,

• Aly, Mostafa Gaafar, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Mostafa Gaafar Aly,

• Speer, Claudius, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Claudius Speer,

• Kälble, Florian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Florian Kälble,

• Nusshag, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Christian Nusshag,

• Pego silva, Luiza, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Luiza Pego silva,

• Sommerer, Claudia, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Claudia Sommerer,

• Hückelhoven-Krauss, Angela, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Angela Hückelhoven-Krauss,

• Mehrabi, Arianeb, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Arianeb Mehrabi,

• Mueller-Tidow, Carsten, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Carsten Mueller-Tidow,

• Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States

Jochen Reiser,

• Zeier, Martin G., Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Martin G. Zeier,

• Schmitt, Michael, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Michael Schmitt,

• Terness, Peter, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Peter Terness,

• Schmitt, Anita, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Anita Schmitt,

• Daniel, Volker, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Volker Daniel,

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⁺CD24^hiCD38^hi 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⁺CD24^hiCD38^hi and IL10⁺CD19⁺CD24^hiCD38^hi 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⁺CD24^hiCD27⁺ memory (P=0.029), and IL10⁺CD19⁺CD24^hiCD27⁺ 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 – TolerogenixX GmbH