Intragraft and Systemic Immune Parameters Discriminating Between Rejection and Long-Term Graft Function in a Preclinical Model of Intestinal Transplantation

Gerlach, Undine; Klöpfel, Maren; Atanasov, Georgi; Polenz, Dietrich; Vogt, Kathrin; Ahrlich, Stefanie; Marksteiner, Marion; Jurisch, Anke; Loddenkemper, Christoph; Reutzel‐Selke, Anja; Sawitzki, Birgit; Pascher, Andreas

doi:10.1097/tp.0000000000001469

Cited by 6 publications

(2 citation statements)

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“…However, only a few studies have reported the association between LBP and rejection after solid organ transplantation. Gerlach et al showed that plasma LBP levels increased during acute and chronic rejections after intestinal transplantation in rats [ 36 ], and Freue et al reported that seven plasma proteins including LBP were increased in recipients with biopsy-proven acute rejection [ 37 ]. A case–control discovery study by the Genome Canada Biomarkers in Transplantation Group showed that LBP was one of the proteomic signatures in the plasma during early acute kidney allograft rejection.…”

Section: Discussionmentioning

confidence: 99%

Urinary Exosomal Cystatin C and Lipopolysaccharide Binding Protein as Biomarkers for Antibody−Mediated Rejection after Kidney Transplantation

et al. 2022

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We aimed to discover and validate urinary exosomal proteins as biomarkers for antibody−mediated rejection (ABMR) after kidney transplantation. Urine and for-cause biopsy samples from kidney transplant recipients were collected and categorized into the discovery cohort (n = 36) and a validation cohort (n = 65). Exosomes were isolated by stepwise ultra-centrifugation for proteomic analysis to discover biomarker candidates for ABMR (n = 12). Of 1820 exosomal proteins in the discovery cohort, four proteins were specifically associated with ABMR: cystatin C (CST3), serum paraoxonase/arylesterase 1, retinol-binding protein 4, and lipopolysaccharide−binding protein (LBP). In the validation cohort, the level of urinary exosomal LBP was significantly higher in the ABMR group (n = 25) compared with the T-cell-mediated rejection (TCMR) group and the no major abnormality (NOMOA) group. Urinary exosomal CST3 level was significantly higher in the ABMR group compared with the control and NOMOA groups. Immunohistochemical staining showed that LBP and CST3 in the glomerulus were more abundant in the ABMR group compared with other groups. The combined prediction probability of urinary exosomal LBP and CST3 was significantly correlated with summed LBP and CST3 intensity scores in the glomerulus and peritubular capillary as well as Banff g + ptc scores. Urinary exosomal CST3 and LBP could be potent biomarkers for ABMR after kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

Urinary Exosomal Cystatin C and Lipopolysaccharide Binding Protein as Biomarkers for Antibody−Mediated Rejection after Kidney Transplantation

et al. 2022

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“…Allograft rejection after kidney transplantation is the main factor affecting the long-term survival of renal allograft ( Gerlach et al, 2017 ; Wang et al, 2017 ; Nunes-Dos-Santos et al, 2020 ). According to its mechanism, rejection episodes following renal transplant can be classified into T-cell-mediated rejection (TCMR) and humoral rejection ( Rodríguez-Perálvarez et al, 2017 ; Haas, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Iguratimod Attenuates Macrophage Polarization and Antibody-Mediated Rejection After Renal Transplant by Regulating KLF4

et al. 2022

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Background: This study aimed to explore the effect and mechanism of iguratimod (IGT) on M1 macrophage polarization and antibody-mediated rejection (ABMR) after renal transplant.Methods: Bioinformatics analysis was performed using three public databases derived from the GEO database. Sprague–Dawley (SD) rats were pre-sensitized with donors of Wistar rats in skin transplantation and a rat renal transplant ABMR model was established from the donors to skin pre-sensitized recipients. Subsequently, IGT was treated on the ABMR model. Routine staining and immunofluorescence (IF) staining were performed to observe the pathological changes in each group and flow cytometry was performed to detect the changes of DSA titers in peripheral blood. In addition, bone-marrow-derived macrophage (BMDM) was extracted and interfered with IGT to explore the effect of IGT in vivo. PCR, IF staining, and Western blot were used to detect the expression of related genes and proteins.Results: Bioinformatics analysis revealed that several immune cells were significantly infiltrated in the ABMR allograft, while M1 macrophage was noticed with the most significance. Results of IF staining and PCR proved the findings of the bioinformatics analysis. Based on this, IGT was observed to significantly attenuate the degree of peritubular capillary vasculitis and arteriolitis in the rat renal transplant ABMR model, whereas it decreases the expression of C4d and reduces the titer of DSA. Results in vitro suggested that M1 macrophage-related transcripts and proteins were significantly reduced by the treatment of IGT in a dose- and time-dependent manner. Furthermore, IGT intervention could remarkably decrease the expression of KLF4.Conclusion: Polarization of M1 macrophages may aggravate ABMR after renal transplant by promoting DSA-mediated endothelial cell injury, and IGT may attenuate the pathogenesis of ABMR by targeting KLF4.

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Small bowel transplant – novel indications and recent progress

Zorzetti

Marino

Sorrenti

et al. 2023

Expert Review of Gastroenterology & Hepatology

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Intragraft and Systemic Immune Parameters Discriminating Between Rejection and Long-Term Graft Function in a Preclinical Model of Intestinal Transplantation

Abstract: We studied acute and chronic rejections in a preclinical model of ITX, which recapitulates clinical findings and highlights the importance of monitoring peripheral T cell activation inhibitor-mitochondrial expression, LBP levels, and antidonor antibodies for revealing rejection.

Cited by 6 publications

References 44 publications

Urinary Exosomal Cystatin C and Lipopolysaccharide Binding Protein as Biomarkers for Antibody−Mediated Rejection after Kidney Transplantation

Urinary Exosomal Cystatin C and Lipopolysaccharide Binding Protein as Biomarkers for Antibody−Mediated Rejection after Kidney Transplantation

Iguratimod Attenuates Macrophage Polarization and Antibody-Mediated Rejection After Renal Transplant by Regulating KLF4

Small bowel transplant – novel indications and recent progress

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