Can Gene Expression Analysis in Zero-Time Biopsies Predict Kidney Transplant Rejection?

URN zum Zitieren dieses Dokuments:: urn:nbn:de:bvb:355-epub-528360
DOI zum Zitieren dieses Dokuments:: 10.5283/epub.52836

Vonbrunn, Eva ; Angeloni, Miriam ; Büttner-Herold, Maike ; Müller-Deile, Janina ; Heller, Katharina ; Bleich, Erik ; Söllner, Stefan ; Amann, Kerstin ; Ferrazzi, Fulvia ; Daniel, Christoph

Lizenz: Creative Commons Namensnennung 4.0 International
PDF - Veröffentlichte Version
(9MB)

Veröffentlichungsdatum dieses Volltextes: 31 Aug 2022 16:05

Alternative Links zum Volltext:DOI Verlag Verlag

Details

Vorschau

Bibliographische Daten exportieren

Zusammenfassung

Zusammenfassung

Zero-time biopsies are taken to determine the quality of the donor organ at the time of transplantation. Histological analyses alone have so far not been able to identify parameters that allow the prediction of subsequent rejection episodes or graft survival. This study investigated whether gene expression analyses of zero-time biopsies might support this prediction. Using a well-characterized cohort of 26 zero-time biopsies from renal transplant patients that include 4 living donor (LD) and 22 deceased donor (DD) biopsies that later developed no rejection (Ctrl, n = 7), delayed graft function (DGF, n = 4), cellular (T-cell mediated rejection; TCMR, n = 8), or antibody-mediated rejection (ABMR, n = 7), we analyzed gene expression profiles for different types of subsequent renal transplant complication. To this end, RNA was isolated from formalin-fixed, paraffin-embedded (FFPE) sections and gene expression profiles were quantified. Results were correlated with transplant data and B-cell, and plasma cell infiltration was assessed by immunofluorescence microscopy. Both principal component analysis and clustering analysis of gene expression data revealed marked separation between LDs and DDs. Differential expression analysis identified 185 significant differentially expressed genes (adjusted p < 0.05). The expression of 68% of these genes significantly correlated with cold ischemia time (CIT). Furthermore, immunoglobulins were differentially expressed in zero-time biopsies from transplants later developing rejection (TCMR + ABMR) compared to non-rejected (Ctrl + DGF) transplants. In addition, immunoglobulin expression did not correlate with CIT but was increased in transplants with previous acute renal failure (ARF). In conclusion, gene expression profiles in zero-time biopsies derived from LDs are markedly different from those of DDs. Pre-transplant ARF increased immunoglobulin expression, which might be involved in triggering later rejection events. However, these findings must be confirmed in larger cohorts and the role of early immunoglobulin upregulation in zero-biopsies needs further clarification.

Nur für Besitzer und Autoren: Kontrollseite des Eintrags

Downloadstatistik

Altmetric

Alternative Statistik (altmetrics)

Weitere Literatur (mittels CORE)

Details

Vorschau

Bibliographische Daten exportieren

Zusammenfassung

Zusammenfassung

Downloadstatistik

Downloads

Alternative Statistik (altmetrics)

Weitere Literatur (mittels CORE)

Universitätsbibliothek