Chronic Allograft Damage (chronic + allograft_damage)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Rat Cytomegalovirus Infection Interferes with Anti-CD4 mAb-(RIB 5/2) Mediated Tolerance and Induces Chronic Allograft Damage

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2006
A. Pascher
In order to assess the role of heterologous immunity on tolerance induction (TI) by signal 1 modification, the influence of rat cytomegalovirus infection (RCMVI) on TI by a non-depleting monoclonal anti-CD4 mAb (monoclonal antibody) (RIB 5/2) in a rat kidney transplant (KTx) model was investigated. Orthotopic rat KTx (Dark Agouty (DA) , Lewis (LEW)) was performed after TI with RIB 5/2 [10 mg/kg body weight (BW); day ,1, 0, 1, 2, 3; i.p. (intraperitoneal route)]. RCMVI (5 × 10E5 Plaque forming units [PFU] i.p.) was simultaneously conducted to KTx, 50 days after KTx, and 14 days before and after KTx. RIB 5/2 induced robust allograft tolerance even across the high-responder strain barrier. RCMVI broke RIB 5/2-induced tolerance regardless of the time of RCMVI but did not induce acute graft failure during the 120 days follow-up. RCMVI induced a significant chronic deterioration of allograft function (p < 0.01) and enhanced morphological signs of chronic allograft damage (p < 0.05). Cellular infiltrates and major histo-compatibility complex (MHC)-expression were more pronounced (p < 0.05) in the infected groups. RCMVI induced not only RCMV-specific T-cell response but also enhanced the frequency of alloreactive T cells. RCMV interferes with anti-CD4 mAb-induced tolerance and leads to chronic allograft damage. The data we presented suggest a potentially important role of viral infections and their prophylaxis in clinical TI protocols. [source]

Wnt Pathway Regulation in Chronic Renal Allograft Damage

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
C. Von Toerne
The Wnt signaling pathway, linked to development, has been proposed to be recapitulated during the progressive damage associated with chronic organ failure. Chronic allograft damage following kidney transplantation is characterized by progressive fibrosis and a smoldering inflammatory infiltrate. A modified, Fischer 344 (RT1lvl) to Lewis (RT1l) rat renal allograft model that reiterates many of the major pathophysiologic processes seen in patients with chronic allograft failure was used to study the progressive disease phenotype and specific gene product expression by immunohistochemistry and transcriptomic profiling. Central components of the Tgfb, canonical Wnt and Wnt-Ca2+ signaling pathways were significantly altered with the development of chronic damage. In the canonical Wnt pathway, Wnt3, Lef1 and Tcf1 showed differential regulation. Target genes Fn1, Cd44, Mmp7 and Nos2 were upregulated and associated with the progression of renal damage. Changes in the Wnt-Ca2+ pathway were evidenced by increased expression of Wnt6, Wnt7a, protein kinase C, Cam Kinase II and Nfat transcription factors and the target gene vimentin. No evidence for alterations in the Wnt planar cell polarity (PCP) pathway was detected. Overall results suggest cross talk between the Wnt and Tgfb signaling pathways during allograft inflammatory damage and present potential targets for therapeutic intervention. [source]

Induction therapy: Why, when, and which agent?

PEDIATRIC TRANSPLANTATION, Issue 3 2010
Leah Krischock
Krischock L, Marks SD. Induction therapy: Why, when, and which agent? Pediatr Transplantation 2010: 14:298,313. © 2010 John Wiley & Sons A/S. Abstract:, The long-term outcome of paediatric transplantation has improved over the last decade with an increase in the armamentarium of immunosuppressive agents. However, the battle against the hostile immune response at the time of and after transplantation continues. Induction therapy can reduce early injury, to optimize the long-term allograft survival. The goal of induction immunosuppression in paediatric transplantation is to permit the use of lower doses of maintenance immunosuppressive agents without increased rates of acute allograft rejection and chronic allograft damage. The aim of this review is to summarize the current literature relating to the use of antibody agents for induction in paediatric solid organ transplantation. [source]

Rat Cytomegalovirus Infection Interferes with Anti-CD4 mAb-(RIB 5/2) Mediated Tolerance and Induces Chronic Allograft Damage

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2006
A. Pascher
In order to assess the role of heterologous immunity on tolerance induction (TI) by signal 1 modification, the influence of rat cytomegalovirus infection (RCMVI) on TI by a non-depleting monoclonal anti-CD4 mAb (monoclonal antibody) (RIB 5/2) in a rat kidney transplant (KTx) model was investigated. Orthotopic rat KTx (Dark Agouty (DA) , Lewis (LEW)) was performed after TI with RIB 5/2 [10 mg/kg body weight (BW); day ,1, 0, 1, 2, 3; i.p. (intraperitoneal route)]. RCMVI (5 × 10E5 Plaque forming units [PFU] i.p.) was simultaneously conducted to KTx, 50 days after KTx, and 14 days before and after KTx. RIB 5/2 induced robust allograft tolerance even across the high-responder strain barrier. RCMVI broke RIB 5/2-induced tolerance regardless of the time of RCMVI but did not induce acute graft failure during the 120 days follow-up. RCMVI induced a significant chronic deterioration of allograft function (p < 0.01) and enhanced morphological signs of chronic allograft damage (p < 0.05). Cellular infiltrates and major histo-compatibility complex (MHC)-expression were more pronounced (p < 0.05) in the infected groups. RCMVI induced not only RCMV-specific T-cell response but also enhanced the frequency of alloreactive T cells. RCMV interferes with anti-CD4 mAb-induced tolerance and leads to chronic allograft damage. The data we presented suggest a potentially important role of viral infections and their prophylaxis in clinical TI protocols. [source]