Intrarenal Complement System Transcripts in Chronic Antibody-Mediated Rejection and Recurrent IgA Nephropathy in Kidney Transplantation

Cernoch, M; Hrubá, Petra; Kollár, Marek; Mrázová, Petra; Stranavova, Lucia; Lodererová, Alena; Honsová, Eva; Viklický, Ondřej

doi:10.3389/fimmu.2018.02310

Cited by 15 publications

(9 citation statements)

References 37 publications

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“…The expressions of the SH2D1B, CX3CR1, IGHG1, IRF4, MS4A1, C5, CD46, and TGFB1 transcripts were higher in the TI of patients with chronic active ABMR; only the expression of the CD14 gene predominated in the glomeruli. The upregulation of complement-associated gene transcripts in chronic ABMR was just recently reported (35). In our study, we showed the TI as a source of upregulated transcripts, including complement ones, in chronic active ABMR.…”

Section: Discussionsupporting

confidence: 82%

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts

et al. 2021

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Molecular assessment of renal allografts has already been suggested in antibody-mediated rejection (ABMR), but little is known about the gene transcript patterns in particular renal compartments. We used laser capture microdissection coupled with quantitative RT-PCR to distinguish the transcript patterns in the glomeruli and tubulointerstitium of kidney allografts in sensitized retransplant recipients at high risk of ABMR. The expressions of 13 genes were quantified in biopsies with acute active ABMR, chronic active ABMR, acute tubular necrosis (ATN), and normal findings. The transcripts were either compartment specific (TGFB1 in the glomeruli and HAVCR1 and IGHG1 in the tubulointerstitium), ABMR specific (GNLY), or follow-up specific (CXCL10 and CX3CR1). The transcriptional profiles of early acute ABMR shared similarities with ATN. The transcripts of CXCL10 and TGFB1 increased in the glomeruli in both acute ABMR and chronic active ABMR. Chronic active ABMR was associated with the upregulation of most genes (SH2D1B, CX3CR1, IGHG1, MS4A1, C5, CD46, and TGFB1) in the tubulointerstitium. In this study, we show distinct gene expression patterns in specific renal compartments reflecting cellular infiltration observed by conventional histology. In comparison with active ABMR, chronic active ABMR is associated with increased transcripts of tubulointerstitial origin.

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Section: Discussionsupporting

confidence: 82%

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts

et al. 2021

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“…The study showed that defective peripheral CD46 gene expression did not correlate with eGFR at sampling, but with a faster annual loss of GFR [ 65 ]. Similarly, Cernoch et al [ 66 ], in a retrospective study of kidney-transplanted patients with IgAN recurrence, showed that there were no associations of eGFR with intrarenal CD46 complement transcripts, however they did describe the association of several intrarenal gene transcripts, including CD55, with CKD stage. In addition, new data coming from genetic and clinical studies are demonstrating a pivotal role of factor H and complement factor H–related proteins (CFHR) in IgAN development and progression [ 67 , 68 ] Deletion of CFHR1–3 was demonstrated to be protective in IgAN and these molecules are competitors of factor H and can efficiently lead to uncontrolled complement activation [ 56 , 69 ].…”

Section: Mechanism Of Diseasementioning

confidence: 99%

Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review of the incidence, risk factors, pathophysiology and management of immunosuppressive therapy

Infante

Rossini

Lorenzo

et al. 2020

Clinical Kidney Journal

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Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications.

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“…The first in vivo studies showed that overexpression of human CD55 and CD59 (hCD55, hCD59) protects mice from impaired kidney function in an experimental renal I/R injury model (Bongoni et al, 2017). A recent retrospective study of 150 patients after kidney transplantation, confirmed that lower intragraft expression of CD55 is a risk factor for rapid progression of chronic renal rejection (Cernoch et al, 2018). A more detailed study of kidney transplantations demonstrated a correlation between promotor polymorphisms in complement-regulatory proteins and graft survival (Michielsen et al, 2018).…”

Section: Accommodation: the Role Of Protective Gene Expression In Ecsmentioning

confidence: 99%

Vascular Signaling in Allogenic Solid Organ Transplantation – The Role of Endothelial Cells

et al. 2020

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Graft rejection remains the major obstacle after vascularized solid organ transplantation. Endothelial cells, which form the interface between the transplanted graft and the host's immunity, are the first target for host immune cells. During acute cellular rejection endothelial cells are directly attacked by HLA I and II-recognizing NK cells, macrophages, and T cells, and activation of the complement system leads to endothelial cell lysis. The established forms of immunosuppressive therapy provide effective treatment options, but the treatment of chronic rejection of solid organs remains challenging. Chronic rejection is mainly based on production of donor-specific antibodies that induce endothelial cell activation-a condition which phenotypically resembles chronic inflammation. Activated endothelial cells produce chemokines, and expression of adhesion molecules increases. Due to this pro-inflammatory microenvironment, leukocytes are recruited and transmigrate from the bloodstream across the endothelial monolayer into the vessel wall. This mononuclear infiltrate is a hallmark of transplant vasculopathy. Furthermore, expression profiles of different cytokines serve as clinical markers for the patient's outcome. Besides their effects on immune cells, activated endothelial cells support the migration and proliferation of vascular smooth muscle cells. In turn, muscle cell recruitment leads to neointima formation followed by reduction in organ perfusion and eventually results in tissue injury. Activation of endothelial cells involves antibody ligation to the surface of endothelial cells. Subsequently, intracellular signaling pathways are initiated. These signaling cascades may serve as targets to prevent or treat adverse effects in antibody-activated endothelial cells. Preventive or therapeutic strategies for chronic rejection can be investigated in sophisticated mouse models of transplant vasculopathy, mimicking interactions between immune cells and endothelium.

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Intrarenal Complement System Transcripts in Chronic Antibody-Mediated Rejection and Recurrent IgA Nephropathy in Kidney Transplantation

Cited by 15 publications

References 37 publications

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts

Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review of the incidence, risk factors, pathophysiology and management of immunosuppressive therapy

Vascular Signaling in Allogenic Solid Organ Transplantation – The Role of Endothelial Cells

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