Cold Ischemia Does Not Interfere With Tolerance Induction

Reutzel‐Selke, Anja; Hartmann, Jan; Brandenburg, Paul; Jurisch, Anke; Francuski, M.; Ulrich, Frank; Kotsch, Katja; Pascher, Andreas; Tullius, Stefan G.; Pratschke, Johann

doi:10.1097/tp.0b013e31819dfb29

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…The same group demonstrated that extended cold ischemia did not interfere with the induction of rat kidney allograft tolerance using anti-CD4 mAb treatment. 17 These findings are in line with our results in porcine recipients of isolated kidney allograft. However, to our knowledge, comparable studies evaluating the effects of brain death on tolerance in heart or lung allograft recipients have not been performed.…”

Section: Discussionsupporting

confidence: 90%

“…Francuski et al (16) showed that donor brain death affected the long term function and histology of rat kidneys transplanted into recipients treated with 10 days of CyA and anti-CD4 mAb therapy, but it did not have an effect on overall graft survival. The same group demonstrated that extended cold ischemia did not interfere with the induction of rat kidney allograft tolerance using anti-CD4 mAb treatment (17). These findings are in line with our results in porcine recipients of isolated kidney allograft.…”

Section: Discussionmentioning

confidence: 99%

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The effects of brain death and ischemia on tolerance induction are organ-specific

Michel

Madariaga

LaMuraglia

et al. 2018

American Journal of Transplantation

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We have previously shown that 12 days of high-dose calcineurin inhibition induced tolerance in MHC inbred miniature swine receiving MHC-mismatched lung, kidney, or co-transplanted heart/kidney allografts. However, if lung grafts were procured from donation after brain death (DBD), and transplanted alone, they were rejected within 19-45 days. Here, we investigated whether donor brain death with or without allograft ischemia would also prevent tolerance induction in kidney or heart/kidney recipients. Four kidney recipients treated with 12 days of calcineurin inhibition received organs from donors rendered brain dead for 4 hours. Six heart/kidney recipients also treated with calcineurin inhibition received organs from donors rendered brain dead for 4 hours, 8 hours, or 4 hours with 4 additional hours of cold storage. In contrast to lung allograft recipients, all isolated kidney or heart/kidney recipients that received organs from DBD donors achieved long-term survival (>100 days) without histologic evidence of rejection. Proinflammatory cytokine gene expression was upregulated in lungs and hearts, but not kidney allografts, after brain death. These data suggest that the deleterious effects of brain death and ischemia on tolerance induction are organ-specific, which has implications for the application of tolerance to clinical transplantation.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

The effects of brain death and ischemia on tolerance induction are organ-specific

Michel

Madariaga

LaMuraglia

et al. 2018

American Journal of Transplantation

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“…Because of frequent late-onset rejection following alemtuzumab, which was attributed to lymphopenia-induced proliferation, the protocol was again modified to include thymoglobulin (Thymoglobulin â , Genzyme, Cambridge, Mass., USA; 7.5 mg/kg BW total dose) and one dose of infliximab (Remicade â , Centocor Inc., Essex Pharma GmbH; 5 mg/kg BW). Infliximab was used to mitigate IRI and to deplete effector memory CD8 + T cells [31,32].…”

Section: Induction Therapymentioning

confidence: 99%

Clinical relevance of thede novoproduction of anti-HLA antibodies following intestinal and multivisceral transplantation

et al. 2014

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Summary Despite a negative pretransplant cross‐match, intestinal transplant recipients can mount humoral immune responses soon after transplantation. Moreover, the development of donor‐specific anti‐HLA antibodies (DSAs) is associated with severe graft injury. Between June 2000 and August 2011, 30 patients (median age 37.6 ± 9.8 years) received isolated intestinal transplantations (ITX, n = 18) or multivisceral transplantations (MVTXs, n = 12) at our center. We screened for human leukocyte antigen (HLA) antibodies pre‐ and post‐transplant. If patients produced DSAs, treatment with plasmapheresis and intravenous immunoglobulin (IVIG) was initiated. In the event of DSA persistence and/or treatment‐refractory rejection, rituximab and/or bortezomib were added. Ten patients developed DSAs and simultaneously showed significant signs of rejection. These patients received plasmapheresis and IVIG. Eight patients additionally received rituximab, and two patients were treated with bortezomib. DSA values decreased upon antirejection therapy in 8 of the 10 patients. The development of DSAs following ITX is often associated with acute rejection. We observed that the number of mismatched antigens and epitopes correlates with the probability of developing de novo DSAs. Early diagnosis and therapy, including B‐cell depletion and plasma cell inhibition, are crucial to preventing further graft injury.

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“…It has also been revealed by Serrick et al that ischemic injury predisposed the lung allograft to acute rejection through the upregulation of MHC class II antigen expression [7]. Reutzel-Selke et al [8] demonstrated that in a rat lung transplantation model, prolonged cold ischemia for 12 hours did not interfere with tolerance induction. Rodríguez et al [9] showed that in the same model, prolonged cold ischemic time of 10 hours was not associated with more severe acute rejection.…”

Section: Introductionmentioning

confidence: 94%

Prolonged Cold Ischemic Time Results in Increased Acute Rejection in a Rat Allotransplantation Model

Xia

Zhang

et al. 2010

Journal of Surgical Research

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Cold Ischemia Does Not Interfere With Tolerance Induction

Cited by 9 publications

References 48 publications

The effects of brain death and ischemia on tolerance induction are organ-specific

The effects of brain death and ischemia on tolerance induction are organ-specific

Clinical relevance of thede novoproduction of anti-HLA antibodies following intestinal and multivisceral transplantation

Prolonged Cold Ischemic Time Results in Increased Acute Rejection in a Rat Allotransplantation Model

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