Analysis of dendritic cells and ischemia-reperfusion changes in postimplantation renal allograft biopsies may serve as predictors of subsequent rejection episodes
Autor: | Vivette D. D'Agati, Lloyd E. Ratner, Govind Bhagat, Glen S. Markowitz, M. A. Hardy, Elena-Rodica Vasilescu, Russel J. Crew, Geo Serban, Ibrahim Batal, Anil Chandraker, Syed A. Husain, Shefali Patel, Demetra Tsapepas, Kasi McCune, Sacha A. De Serres, Sumit Mohan, Jan M. Herter, Jae-Hyung Chang |
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Rok vydání: | 2018 |
Předmět: |
Adult
Graft Rejection Male 0301 basic medicine Pathology medicine.medical_specialty Time Factors Myeloid Biopsy Ischemia Kidney Risk Assessment Antigens CD1 Young Adult 03 medical and health sciences Cell Movement Predictive Value of Tests Risk Factors Cause of Death Living Donors medicine Humans Acute tubular necrosis Aged Glycoproteins Retrospective Studies Cause of death business.industry Immunogenicity Graft Survival Alloimmunity Dendritic Cells Dendritic cell Middle Aged Allografts medicine.disease Kidney Transplantation Tissue Donors Treatment Outcome 030104 developmental biology medicine.anatomical_structure Nephrology Reperfusion Injury Female business Biomarkers |
Zdroj: | Kidney International. 93:1227-1239 |
ISSN: | 0085-2538 |
DOI: | 10.1016/j.kint.2017.12.015 |
Popis: | Ischemia-reperfusion injury increases allograft immunogenicity and enhances myeloid dendritic cell maturation and trafficking to recipient's secondary lymphoid tissue. Here, we used postreperfusion biopsies from patients who received kidney allografts from deceased donors between 2006 and 2009 to assess the impact of ischemia-reperfusion damage and myeloid dendritic cell density on subsequent allograft rejection episodes. Histologic changes of severe ischemia-reperfusion damage in postreperfusion biopsies were found to be associated with subsequent rejection episodes and suboptimal allograft survival. Using BDCA-1 as a marker of myeloid dendritic cells, postreperfusion biopsies from deceased donors had lower dendritic cell density compared to postreperfusion biopsies from living donors or normal controls. This suggests a rapid emigration of donor dendritic cells out of the allograft. In our cohort, low dendritic cell density was associated with a subsequent increase in rejection episodes. However, it appears that the donor's cause of death also influenced dendritic cell density. Therefore, we assessed the additive impact of severe ischemia-reperfusion changes and low dendritic cell density on subsequent rejection. The aforementioned combination was a powerful and independent predictor of allograft rejection. Thus, our data highlight the prognostic value of histopathologic changes associated with ischemia-reperfusion in postreperfusion biopsies and suggest a rapid posttransplant emigration of myeloid dendritic cells out of the allograft to enhance alloimmunity. These findings may provide a rationale for minimizing ischemia-reperfusion injury and therapeutic targeting of donor-derived dendritic cells to promote rejection-free allograft survival. |
Databáze: | OpenAIRE |
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