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  1. Article ; Online: Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants

    Eva Vonbrunn / Tajana Ries / Stefan Söllner / Janina Müller-Deile / Maike Büttner-Herold / Kerstin Amann / Christoph Daniel

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Abstract In renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are initiated. Using allograft biopsies of a well- ... ...

    Abstract Abstract In renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are initiated. Using allograft biopsies of a well-characterized cohort of 28 renal transplant patients with no rejection (Ctrl), delayed graft function (DGF), acute T-cell-mediated (TCMR) or antibody-mediated rejection (ABMR) we analyzed differences in complement reaction. For that mRNA was isolated from FFPE sections, quantified with a multiplex gene expression panel and correlated with transplant conditions and follow-up of patients. Additionally, inflammatory cells were quantified by multiplex immunohistochemistry. In allograft biopsies with TCMR and ABMR gene expression of C1QB was 2-4 fold elevated compared to Ctrl. In TCMR biopsies, mRNA counts of several complement-related genes including C1S, C3, CFB and complement regulators CFH, CR1 and SERPING1 were significantly increased compared to Ctrl. Interestingly, expression levels of about 75% of the analyzed complement related genes correlated with cold ischemia time (CIT) and markers of inflammation. In conclusion, this study suggest an important role of complement in transplant pathology which seems to be at least in part triggered by CIT. Multiplex mRNA analysis might be a useful method to refine diagnosis and explore new pathways involved in rejection.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Can Gene Expression Analysis in Zero-Time Biopsies Predict Kidney Transplant Rejection?

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

    Frontiers in Medicine, Vol

    2022  Volume 9

    Abstract: 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 ... ...

    Abstract 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 ...
    Keywords kidney transplantation ; zero-time biopsy ; mRNA expression ; inflammation ; outcome ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Significance of Glomerular Immune Reactivity in Time Zero Biopsies for Allograft Survival Beyond IgA

    Eva Vonbrunn / Sofya Serikova / Christoph Daniel / Kerstin Amann / Johannes Schödel / Björn Buchholz / Fulvia Ferrazzi / Katharina Heller / Hendrik Apel / Maike Büttner-Herold

    Frontiers in Medicine, Vol

    2021  Volume 8

    Abstract: The quality of a renal transplant can influence the clinical course after transplantation. Glomerular immune reactivity in renal transplants has previously been described, focusing particularly on IgA, and has been shown to disappear in most cases ... ...

    Abstract The quality of a renal transplant can influence the clinical course after transplantation. Glomerular immune reactivity in renal transplants has previously been described, focusing particularly on IgA, and has been shown to disappear in most cases without affecting the outcome. Here, we describe a cohort of time zero biopsies with regard to glomerular immune reactivity and implications for histomorphology and follow-up. 204 Time zero biopsies were analyzed by immunohistochemistry for glomerular immune reactivity. Time zero and 1-year biopsies were evaluated for histomorphological changes, which, together with clinical and follow-up data, were assessed for associations with glomerular immune profiles. Nearly half of the analyzed time zero biopsies showed glomerular immune reactivity with mesangial C3 being the most common (32.9%), followed by IgA (13.7%) and fullhouse patterns (6.9%). Strong C3 deposits (C3high) were only observed in deceased transplants. In the majority of cases immune reactivity was undetectable in follow-up biopsies and had no adverse effect on transplant function in follow-up of 5 years. In kidney pairs transplanted to different recipients a strong concordance of immune profiles in both kidneys was observed. Moreover, an association of male donor sex and deceased donor transplantation with the presence of immune reactivity was observed. In conclusion, glomerular immune reactivity is a very frequent finding in time zero biopsies, which seems to be determined by donor parameters including male sex and deceased donor transplants. It had no adverse impact on transplant function in 5-year follow-up. Glomerular immune reactivity in time zero biopsies, therefore, does not appear to indicate an inferior quality of the transplant.
    Keywords complement ; renal tranplantation ; time zero biopsy ; transplant quality ; immune reactivity ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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