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Allograft Survival (allograft + survival)
Kinds of Allograft Survival Selected AbstractsInduction of Indoleamine 2,3-Dioxygenase by Gene Delivery in Allogeneic Islets Prolongs Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010H. Dellê Indoleamine 2,3-dioxygenase (IDO), an enzyme that plays a critical role in fetomaternal tolerance, exerts immunoregulatory functions suppressing T-cell responses. The aims of this study were to promote IDO expression in rat islets using a nonviral gene transfer approach, and to analyze the effect of the in vivo induction of IDO in a model of allogeneic islet transplantation. The IDO cDNA was isolated from rat placenta, subcloned into a plasmid and transfected into rat islets using Lipofectamine. The efficiency of transfection was confirmed by qRT-PCR and functional analysis. The in vivo effect of IDO expression was analyzed in streptozotocin-induced diabetic Lewis rats transplanted with allogeneic islets under the renal capsule. Transplantation of IDO-allogeneic islets reversed diabetes and maintained metabolic control, in contrast to transplantation of allogeneic nontransfected islets, which failed shortly after transplantation in all animals. Graft survival of allograft islets transfected with IDO transplanted without any immunosuppression was superior to that observed in diabetic rats receiving nontransfected islets. These data demonstrated that IDO expression induced in islets by lipofection improved metabolic control of streptozotocin-diabetic rats and prolonged allograft survival. [source] Focal C4d+ in Renal Allografts Is Associated with the Presence of Donor-Specific Antibodies and Decreased Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009R. L. Kedainis Diffuse peritubular capillary C4d deposition in renal allograft biopsies is associated with donor-specific antibodies (DSA) and graft failure. The significance of focal C4d+ is unclear. We reviewed 368 biopsies from 301 patients performed for renal dysfunction or proteinuria over 5 years. Diffuse C4d+, focal C4d+ and C4d- detected by immunofluorescence occurred in 9.5%, 20.9% and 69.4% of biopsies, respectively. Patients were similar in gender, age, cause of renal disease, donor source, HLA mismatch, serum creatinine at baseline and interval from transplantation to biopsy. Diffuse and focal C4d+ were associated with acute cellular rejection (p < 0.001). Transplant glomerulopathy was associated with diffuse C4d+. DSA at the time of biopsy, were positive in 79.3% of diffusely C4d+ patients, 68.8% of those with focal C4d+ (p = 0.27) and 9.9% of patients with C4d- (p < 0.001, compared to either the focal or diffuse groups, respectively). Allograft survival at 40 months was lower in diffuse C4d+ compared to the C4d- group (p = 0.014), but not when compared to the focal C4d+ group. There was a clear trend toward worse graft survival in patients with focal C4d+ in this time interval, but focal C4d+ compared to both diffuse C4d+ and C4d-groups was not statistically significant (p = 0.08). [source] Effects of Donor Age and Cell Senescence on Kidney Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009A. Melk The biological processes responsible for somatic cell senescence contribute to organ aging and progression of chronic diseases, and this may contribute to kidney transplant outcomes. We examined the effect of pre-existing donor aging on the performance of kidney transplants, comparing mouse kidney isografts and allografts from old versus young donors. Before transplantation, old kidneys were histologically normal, but displayed an increased expression of senescence marker p16INK4a. Old allografts at day 7 showed a more rapid emergence of epithelial changes and a further increase in the expression of p16INK4a. Similar but much milder changes occurred in old isografts. These changes were absent in young allografts at day 7, but emerged by day 21. The expression of p16INK4a remained low in young kidney allografts at day 7, but increased with severe rejection at day 21. Isografts from young donors showed no epithelial changes and no increase in p16INK4a. The measurements of the alloimmune response,infiltrate, cytology, expression of perforin, granzyme B, IFN-, and MHC,were not increased in old allografts. Thus, old donor kidneys display abnormal parenchymal susceptibility to transplant stresses and enhanced induction of senescence marker p16INK4a, but were not more immunogenic. These data are compatible with a key role of somatic cell senescence mechanisms in kidney transplant outcomes by contributing to donor aging, being accelerated by transplant stresses, and imposing limits on the capacity of the tissue to proliferate. [source] Portal Venous Donor-Specific Transfusion in Conjunction with Sirolimus Prolongs Renal Allograft Survival in Nonhuman PrimatesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009K. K. Dhanireddy Pretransplant exposure to donor antigen is known to modulate recipient alloimmunity, and frequently results in sensitization. However, donor-specific transfusion (DST) can have a protolerant effect that is dependent on route, dose and coadministered immunosuppression. Rodent studies have shown in some strain combinations that portal venous (PV) DST alone can induce tolerance, and uncontrolled clinical use of PVDST has been reported. In order to determine if pretransplant PVDST has a clinically relevant salutary effect, we studied it and the influence of concomitant immunosuppression in rhesus monkeys undergoing renal allotransplantation. Animals received PVDST with unfractionated bone marrow and/or tacrolimus or sirolimus 1 week prior to transplantation. Graft survival was assessed without any posttransplant immunosuppression. PVDST alone or in combination with tacrolimus was ineffective. However, PVDST in combination with sirolimus significantly prolonged renal allograft survival to a mean of 24 days. Preoperative sirolimus alone had no effect, and peripheral DST with sirolimus prolonged graft survival in 2/4 animals, but resulted in accelerated rejection in 2/4 animals. These data demonstrate that PVDST in combination with sirolimus delays rejection in a modest but measurable way in a rigorous model. It may thus be a preferable method for donor antigen administration. [source] Neutralizing IL-7 Promotes Long-Term Allograft Survival Induced by CD40/CD40L Costimulatory BlockadeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2006Y. Wang Memory T cells are somewhat resistant to immunosuppresion. They therefore pose a threat to inducing long-term allograft survival. IL-7 is essential for memory T-cell generation. Here, we investigated whether neutralizing IL-7 promotes allograft survival. We found that neutralizing IL-7 alone did not significantly prolong allograft survival. However, blocking both IL-7 and CD154 signaling synergistically prolonged allograft survival. In contrast, neutralizing IL-2 failed to further prolong allograft survival induced by CD40/CD154 costimulatory blockade. Allospecific memory CD8+ T-cell generation was severely impaired under the treatment of anti-IL-7 plus anti-CD154 Ab while administering recombinant IL-7 enhanced CD8+ memory generation even under donor-specific transfusion plus anti-CD154 Ab treatment. Neutralizing IL-7, but not IL-2, together with blocking CD154 synergistically suppressed the proliferation of naïve/effector CD8+ T cells infiltrating grafts. Nevertheless, neutralizing IL-7 did not alter regulatory T-cell generation while neutralizing IL-2 suppressed their generation. Hence, targeting IL-7 represents a new strategy to prolong allograft survival by acting on both naïve and memory T cells. Long-term allograft survival may be achieved by neutralizing IL-7 plus CD40/CD154 blockade, since CD40/CD154 costimulatory blockade prevents acute rejection while neutralizing IL-7 suppresses the generation of memory T cells that persist and mediate late or chronic rejection. [source] Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2005Cristiam M. Alvarez The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (,9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vß usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR Vß families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells. [source] Feline Immunodeficiency Virus-Mediated Viral Interleukin-10 Gene Transfer Prolongs Non-Vascularized Cardiac Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2003Shuang Fu Previous experiments demonstrated plasmid-, retroviral-, or adenoviral-mediated vIL-10 gene transfer could prolong allograft survival, but transgene expression was rapidly extinguished. Feline immunodeficiency virus (FIV) can integrate into genomic DNA of nondividing cells, resulting in indefinite transgene expression. We hypothesized FIV-mediated gene transfer could provide long-term gene expression, and improved allograft survival. FIV-vIL-10 and FIV-,-gal were produced using the FELIX vector system. With vector transfer to syngeneic cardiac grafts, ,-galactosidase reporter gene expression was noted as early as day 5, was strongly expressed at days 10 and 20, and persisted for 50 days after transplantation. For allografts, FIV-vIL-10 gene transfer more than doubled mean survival from 10 ± 1.6 to 22.3 ± 3 days. When combined with other immunosuppressants, such as anti-CD40L mAb, FTY720, or anti-CD3 mAb, the mean survival times were prolonged to 27 ± 4.6 days, 27.8 ± 4.6 days, and 45.5 ± 4.9 days, respectively. Multiple chemokine and chemokine receptor genes were induced by ischemia-reperfusion injury in syngeneic grafts, and in allogeneic grafts more genes were induced and to a greater degree. In allogeneic grafts transduced with FIV-IL-10, a number of the chemokine genes were suppressed. Therefore, FIV virus-mediated vIL-10 gene transfer prolongs allograft survival and, in combination with other agents, produces an additive effect. [source] The Relationship Between Donor Age and Cadaveric Renal Allograft Survival Is Modified by the Recipient's Blood PressureAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2003Fernando G. Cosio Increasing donor age correlates with reduced renal allograft survival. In this study we analyzed variables that may modify this relationship. The study included 1285 cadaveric kidney allograft recipients followed for 7.2 + 4.5 years. By Cox, increasing donor age beyond 30 years was associated with significant increases in the hazard ratio for graft loss [age 31,46, hazard ratio (HR) =,1.4, p = 0.02; 46,60, HR = 1.55, p = 0.008; > 60, HR = 1.68, p = 0.03]. Increasing donor age was significantly associated with: older and heavier recipients; higher creatinine and blood pressure (BP) 6 months post-transplant; and lower total cyclosporine dose during the first year. Of interest, the 6-month serum creatinine and the BP level modified significantly the relationship between age and survival. Thus, increasing donor age was significantly related to reduced graft survival only in patients with a 6-month creatinine <,2 mg/dL. Furthermore, donor age related significantly to graft survival only among patients with higher BP levels 6 month post transplant. It is concluded that increasing donor age is associated with reduced cadaveric graft survival, but that relationship is significantly modified by graft function and BP. These data suggest that poorly functioning kidneys have reduced survival irrespective of age. Furthermore, elevated BP levels may have a particularly negative effect on the survival of older grafts. [source] Survival of ovarian allografts in an experimental animal modelPEDIATRIC TRANSPLANTATION, Issue 6 2007Roger G. Gosden Abstract: Transplantation of ovarian tissue is a promising strategy for fertility preservation in young cancer patients with premature ovarian failure if they have cryopreserved their own tissue before undergoing gonadotoxic treatment. However, extension of ovary donation to children and adults seeking treatment for hypogonadism is controversial unless the tissue does not provoke an immune reaction or specific tolerance can be safely and effectively achieved. The survival of heterotopic ovarian allografts was tested in a mouse model. Isografts were placed under the kidney capsule of ovariectomized animals differing at the H-2 haplotype (H-2d or H-2k). Within three wk, and in contrast to isografts, the allografts were rejected, although their survival was extended when donor and host strains shared the same haplotype (H-2k). Allograft survival was not improved if the tissue was implanted orthotopically. When monoclonal antibodies to CD4 antigens were administered at doses exceeding those effective for long-term tolerance to cardiac allografts, graft survival was prolonged in one of two strain combinations, but they failed to restore fertility. These results indicate that the ovary is not an immunologically privileged organ, as the older literature suggested, and chronic immunosuppression is likely to be required for ovarian allografts in clinical settings. [source] G protein ,3 subunit 825T genotype is not associated with differing outcome in pediatric renal transplant recipientsPEDIATRIC TRANSPLANTATION, Issue 2 2002Berthold Hocher Recent studies have identified a novel polymorphism (C825T) of the gene encoding the ,3 subunit of heterotrimeric G proteins (GNB3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. The donor GNB3 825TT genotype was associated with reduced kidney allograft survival in adults. We examined (in 100 Caucasian pediatric renal transplant recipients) whether the GNB3 (C825T) polymorphism was associated with disease progression and outcome after renal transplantation. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal transplantation, and the population was divided into two groups of equal size, before and after transplantation, according to the slope. The observed frequencies were 57 for the CC, 33 for the CT, and 10 for the TT haplotype. For comparison, 738 consecutive newborn babies with the same ethnic background were typed in the same hospital. Allele frequencies were statistically not significantly different (chi-square test, p =,0.1327). When dividing the pediatric renal transplant recipients into two groups with regard to the slope of 1/creatinine, both before and after renal transplantation, the observed proportions were CC 26, CT 17, and TT 7 in the group with the poorer slope and CC 31, CT 16, and TT 3 in the group with the better slope before renal transplantation (not significant [NS], chi-square test, p =,0.1777). The observed proportions after renal transplantation were CC 26, CT 16, and TT 8 in the group with the poorer slope and CC 31, CT 15, and TT 4 in the group with the better slope, respectively (NS, chi-square test, p =,0.167). Allograft survival was not associated with the T allele. In conclusion, in a sizeable number of pediatric renal transplant recipients the GNB3 C825T polymorphism was found not to be a genetic risk factor for end-stage kidney disease. In addition, kidney graft function and survival was also found not to be associated with a recipient GNB3 C825T polymorphism. [source] Focal C4d+ in Renal Allografts Is Associated with the Presence of Donor-Specific Antibodies and Decreased Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009R. L. Kedainis Diffuse peritubular capillary C4d deposition in renal allograft biopsies is associated with donor-specific antibodies (DSA) and graft failure. The significance of focal C4d+ is unclear. We reviewed 368 biopsies from 301 patients performed for renal dysfunction or proteinuria over 5 years. Diffuse C4d+, focal C4d+ and C4d- detected by immunofluorescence occurred in 9.5%, 20.9% and 69.4% of biopsies, respectively. Patients were similar in gender, age, cause of renal disease, donor source, HLA mismatch, serum creatinine at baseline and interval from transplantation to biopsy. Diffuse and focal C4d+ were associated with acute cellular rejection (p < 0.001). Transplant glomerulopathy was associated with diffuse C4d+. DSA at the time of biopsy, were positive in 79.3% of diffusely C4d+ patients, 68.8% of those with focal C4d+ (p = 0.27) and 9.9% of patients with C4d- (p < 0.001, compared to either the focal or diffuse groups, respectively). Allograft survival at 40 months was lower in diffuse C4d+ compared to the C4d- group (p = 0.014), but not when compared to the focal C4d+ group. There was a clear trend toward worse graft survival in patients with focal C4d+ in this time interval, but focal C4d+ compared to both diffuse C4d+ and C4d-groups was not statistically significant (p = 0.08). [source] Function of indoleamine 2,3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2006Abstract Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-, and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts. [source] Long-term outcome of human leukocyte antigen mismatching in liver transplantation: Results of the national institute of diabetes and digestive and kidney diseases liver transplantation database,,HEPATOLOGY, Issue 3 2008Vijayan Balan A perfect or nearly perfect human leukocyte antigen (HLA) match has been associated with better immediate and long-term survival of diseased donor kidney transplants. However, the effect of HLA matching for hepatic allografts remains poorly defined. Using data from the National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, we investigated the association between HLA mismatches and hepatic allograft survival, disease recurrence, and immunosuppression interactions. A, B, and DR loci were used to calculate total mismatch scores of 0 (no mismatches in any loci) to 6 (mismatches in all loci). Seven hundred ninety-nine adults (male, 55%; female, 45%) underwent 883 liver transplants. The 10-year graft survival according to total mismatch score was as follows: 0-2, 60%; 3-4, 54%; and 5-6, 57%. There was a negative effect of mismatching at the A locus on patient survival, with shorter survival for patients with 1 or 2 mismatches compared with 0 mismatches [P = 0.05, hazard ratio (HR) = 1.6]. Patients on tacrolimus with 1 or 2 mismatches at B or DR loci appeared to have increased rates of patient and graft survival compared to patients with 0 mismatches, with the appearance of a protective effect of tacrolimus (HR = 0.67). The effect of HLA mismatching was more pronounced on certain disease recurrences. DR-locus mismatch increased recurrence of autoimmune hepatitis (P = 0.01, HR = 4.2) and primary biliary cirrhosis (P = 0.04, HR = 2). Mismatch in the A locus was associated with more recurrence of hepatitis C virus (P = 0.01, HR = 1.6) and primary sclerosing cholangitis (P = 0.03, HR = 2.9). Conclusion: Mismatching at the A locus decreases patient survival in liver transplant recipients, and mismatching at the DR and A loci affects recurrence of autoimmune liver diseases and hepatitis C, respectively. (HEPATOLOGY 2008.) [source] Chemokine receptor-dependent alloresponsesIMMUNOLOGICAL REVIEWS, Issue 1 2003Wayne W. Hancock Summary:, Immunologists have typically viewed alloreactivity schematically as a function of antigen presentation, expansion of alloreactive T and B cells within regional lymphoid tissues, and cellular infiltration and destruction of an allograft. Actual details of the steps between immune activation and accumulation of effector cells within a graft typically have not received much attention. However, just how cells ,know' to move to and migrate within a graft or not is proving to be of increasing interest, as the chemokine-dependent mechanisms underlying leukocyte recruitment to a transplant are dissected. Experimentally, chemokine receptor targeting can prolong or induce permanent allograft survival, despite preservation of alloresponses within secondary lymphoid tissues, whereas current immunosuppressive protocols have only modest effects on chemokine production and leukocyte homing. Recent knowledge of the chemokine-dependent nature of allograft rejection, acceptance, and tolerance induction are presented as a basis for understanding the rationale for preclinical trials of chemokine receptor-targeted therapies currently underway in primate recipients of solid organ allografts. [source] Immunomodulation by mesenchymal stem cells and clinical experienceJOURNAL OF INTERNAL MEDICINE, Issue 5 2007K. Le Blanc Abstract Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders. [source] Complement component C3 allotypes and outcomes in liver transplantationLIVER TRANSPLANTATION, Issue 2 2010Navdeep Dhillon The complement system has been implicated in the pathogenesis of liver diseases. Human complement component C3 (C3) exists as 2 allotypes, fast (F) and slow (S). We conducted a study to address the influence of these alleles on ischemia-reperfusion (IR) injury and graft survival in liver transplant recipients. Four hundred thirty patients receiving liver transplants from 2000 to 2004 were included. C3 allotypes of 296 donor-recipient pairs were determined and correlated with clinical outcomes. Four groups were analyzed according to the C3 genotype: C3 SS donor and recipient, C3 FS or C3 FF donor and C3 SS recipient, C3 SS donor and C3 FS or C3 FF recipient, and C3 FS or C3 FF donor and recipient. Baseline characteristics of the 4 groups were similar. The mean follow-up time was 4.3 ± 2.2 years. The 4 groups had similar rates of IR injury (P = 0.16). The hazard ratios for liver allograft survival in the C3 SS donor and recipient group in comparison with the other 3 groups (C3 FS or C3 FF donor and C3 SS recipient, C3 SS donor and C3 FS or C3 FF recipient, and C3 FS or C3 FF donor and recipient) were not significantly different: 1.13 (P = 0.60), 0.99 (P = 0.97), and 1.02 (P = 0.95), respectively. In conclusion, donor and recipient C3 genotypes are not associated with liver transplantation outcomes. Liver Transpl 16:198,203, 2010. © 2010 AASLD. [source] Factors that identify survival after liver retransplantation for allograft failure caused by recurrent hepatitis C infectionLIVER TRANSPLANTATION, Issue 12 2004Guy W. Neff Hepatitis C virus (HCV) is becoming the most common indication for liver retransplantation (ReLTx). This study was a retrospective review of the medical records of liver transplant patients at our institution to determine factors that would identify the best candidates for ReLTx resulting from allograft failure because of HCV recurrence. The patients were divided into 2 groups on the basis of indication for initial liver transplant. Group 1 included ReLTx patients whose initial indication for LTx was HCV. Group 2 included patients who received ReLTx who did not have a history of HCV. We defined chronic allograft dysfunction (AD) as patients with persistent jaundice (> 30 days) beginning 6 months after primary liver transplant in the absence of other reasons. HCV was the primary indication for initial orthotopic liver transplantation (OLT) in 491/1114 patients (44%) from July 1996 to February 2004. The number of patients with AD undergoing ReLTx in Groups 1 and 2 was 22 and 12, respectively. The overall patient and allograft survival at 1 year was 50% and 75% in Groups 1 and 2, respectively (P = .04). The rates of primary nonfunction and technical problems after ReLTx were not different between the groups. However, the incidence of recurrent AD was higher in Group 1 at 32% versus 17% in Group 2 (P = .04). Important factors that predicted a successful ReLTx included physical condition at the time of ReLTx (P = .002) and Child-Turcotte-Pugh score (P = .008). In conclusion, HCV is associated with an increased incidence of chronic graft destruction with a negative effect on long-term results after ReLTx. The optimum candidate for ReLTx is a patient who can maintain normal physical activity. As the allograft shortage continues, the optimal use of cadaveric livers continues to be of primary importance. The use of deceased donor livers in patients with allograft failure caused by HCV remains a highly controversial issue. (Liver Transpl 2004;10:1497,1503.) [source] Effect of Baohuoside-1 aglycone and tacrolimus monotherapy and combination therapy on prevention of acute heart allograft rejection in the ratMICROSURGERY, Issue 4 2007Shijie Qi M.D. Baohuoside-1 (B-1), a recently introduced novel immunosuppressant that was proved to be potent in inhibition of T and B cell proliferation and B-1, also prevents cardiac allograft rejection in rodents. The present study further proved that monotherapy of B-1's analogue B-1 aglycone effectively prolongs cardiac allograft survival and combination therapy of B-1 aglycone with tacrolimus (FK506) produces synergistic effect in prevention acute cardiac allograft rejection in the rat. © 2007 Wiley-Liss, Inc. Microsurgery 2007. [source] Administration of dendritic cells modified by RNA interference prolongs cardiac allograft survivalMICROSURGERY, Issue 4 2007Jianbin Xiang M.D. Systemic administration of immature donor-dendritic cells (DC) that are deficient in co-stimulatory molecules delays the onset of allograft rejection. However, it is not easy to control culture condition and guarantee that the administered DC are in the immature stages, which obviously affects their therapeutic effect. In this study, we attempted to inhibit expression of CD86 on DC using an RNA interference technology. The function of CD86low DC was determined by the influence on their capacity to stimulate T cell proliferation and by the effect of DC systemic administration on survival of cardiac allografts. CD86low DC stimulated low T cell proliferative responses in vitro and administration of CD86low DC prolonged survival of heart allografts in vivo. These results suggest that RNA interference is a useful approach to modify DC function, which has potentials for clinical application. © 2007 Wiley-Liss, Inc. Microsurgery 2007. [source] Induction therapy: Why, when, and which agent?PEDIATRIC TRANSPLANTATION, Issue 3 2010Leah 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] Long-term outcome following pediatric liver transplantation for metabolic disordersPEDIATRIC TRANSPLANTATION, Issue 2 2010Terrell Stevenson Stevenson T, Millan MT, Wayman K, Berquist WE, Sarwal M, Johnston EE, Esquivel CO, Enns GM. Long-term outcome following pediatric liver transplantation for metabolic disorders. Pediatr Transplant 2010:14:268,275. © 2009 John Wiley & Sons, A/S. Abstract:, In order to determine long-term outcome, including survival, growth and development, following liver transplantation in children with metabolic disorders, we retrospectively reviewed charts of 54 children with metabolic disorders evaluated from 1989,2005 for presenting symptoms, transplantation timing and indications, survival, metabolic parameters, growth, and development. Thirty-three patients underwent liver transplantation (12 received combined liver,kidney transplants) at a median age of 21 months. At a median follow-up of 3.6 yr, patient survival was 100%, and liver and kidney allograft survival was 92%, and 100%, respectively. For the group as a whole, weight Z scores improved and body mass index at follow-up was in the normal range. Two yr post-transplantation, psychomotor development improved significantly (p < 0.01), but mental skills did not; however, both indices were in the low-normal range of development. When compared to patients with biliary atresia, children with metabolic disorders showed significantly lower mental developmental scores at one and two yr post-transplantation (p < 0.05), but psychomotor developmental scores were not significantly different. We conclude that, in patients with metabolic disorders meeting indications for transplantation, liver transplantation or combined liver,kidney transplantation (for those with accompanying renal failure) is associated with excellent long-term survival, improved growth, and improved psychomotor development. [source] Changing trends in pediatric transplantation: 2001 Annual Report of the North American Pediatric Renal Transplant Cooperative StudyPEDIATRIC TRANSPLANTATION, Issue 4 2003Mark R. Benfield This cooperative group now includes over 150 participating medical centers in the United States, Canada, Mexico, and Costa Rica. This report covers the years from 1987 through 2001 and includes data on 7545 renal transplants in 6878 patients. This report demonstrates changing trends in many areas of pediatric transplantation including increasing numbers of African American and Hispanic children receiving transplantation, remarkable improvements in the rate of acute rejection, rejection reversal, and short- and long-term allograft survival. In the most recent cohorts of patients, we now see that 1-yr allograft survival is no different in cadaver donor compared to living donor recipients and in infants compared to all other age groups. However, this analysis also reveals areas of continued challenges including inferior outcomes in African American and adolescent populations, chronic rejection, and the adverse effects of immunosuppression. [source] Limited surgical interventions in children with posterior urethral valves can lead to better outcomes following renal transplantationPEDIATRIC TRANSPLANTATION, Issue 5 2002Leah Bartsch Abstract: There is currently no consensus as to the most appropriate means by which children with posterior urethral valves (PUV) are to be managed prior to transplantation. We compared (i) renal allograft survival and function in patients with PUV vs. those with non-obstructive causes of ESRD and (ii) graft outcomes in children who had limited interventions (Group 1) vs. those with more extensive urologic surgeries to decompress the urinary tract (Group 2). Twenty-six pediatric renal transplant recipients had ESRD due to PUV (Group 1, n = 16; Group 2, n = 10). The study group was compared to 23 matched controls with ESRD due to non-obstructive causes. Five yr patient and graft survival was similar in all patients with PUV (Groups 1 and 2) when compared to all other kidney recipients in the transplant program, 96.2% vs. 98.0% and 87.5% vs. 87.0%, respectively. Although calculated creatinine clearance (Ccr), was similar between the PUV group and controls for the first 4 yr, the 5 yr graft function was significantly lower in the PUV group. (53.7 ± 15.7 vs. 70.2 ± 21.0 mL/min/1.73 m2; p = 0.03). When the two PUV groups were compared, graft survival was equivalent, but graft function was significantly better at 5 yr in Group 1(60.4 ± 10.8 vs. 33.8 ± 9.3 mL/min/1.73 m2; p = 0.02). Thus, patients with PUV managed by a limited intervention approach of vesicostomy with delayed valve ablation or primary valve ablation, had better outcomes. When ESRD is virtually certain, additional pre-transplant surgeries affecting the urinary tract should be avoided. [source] G protein ,3 subunit 825T genotype is not associated with differing outcome in pediatric renal transplant recipientsPEDIATRIC TRANSPLANTATION, Issue 2 2002Berthold Hocher Recent studies have identified a novel polymorphism (C825T) of the gene encoding the ,3 subunit of heterotrimeric G proteins (GNB3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. The donor GNB3 825TT genotype was associated with reduced kidney allograft survival in adults. We examined (in 100 Caucasian pediatric renal transplant recipients) whether the GNB3 (C825T) polymorphism was associated with disease progression and outcome after renal transplantation. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal transplantation, and the population was divided into two groups of equal size, before and after transplantation, according to the slope. The observed frequencies were 57 for the CC, 33 for the CT, and 10 for the TT haplotype. For comparison, 738 consecutive newborn babies with the same ethnic background were typed in the same hospital. Allele frequencies were statistically not significantly different (chi-square test, p =,0.1327). When dividing the pediatric renal transplant recipients into two groups with regard to the slope of 1/creatinine, both before and after renal transplantation, the observed proportions were CC 26, CT 17, and TT 7 in the group with the poorer slope and CC 31, CT 16, and TT 3 in the group with the better slope before renal transplantation (not significant [NS], chi-square test, p =,0.1777). The observed proportions after renal transplantation were CC 26, CT 16, and TT 8 in the group with the poorer slope and CC 31, CT 15, and TT 4 in the group with the better slope, respectively (NS, chi-square test, p =,0.167). Allograft survival was not associated with the T allele. In conclusion, in a sizeable number of pediatric renal transplant recipients the GNB3 C825T polymorphism was found not to be a genetic risk factor for end-stage kidney disease. In addition, kidney graft function and survival was also found not to be associated with a recipient GNB3 C825T polymorphism. [source] Detection of urinary biomarkers for early diagnosis of acute renal allograft rejection by proteomic analysisPROTEOMICS - CLINICAL APPLICATIONS, Issue 6 2009Xiongfei Jia Abstract Acute allograft rejection has been recognized as a major impediment to improved success in renal transplantation. Timely detection and control of rejection are very important for the improvement in long-term renal allograft survival. Thus, biomarkers for early diagnosis of acute rejection are required urgently to clinical medication. This study seeks to search for such biomarker candidates by comparing patients' pre-treatment urinary protein profiling with their post-treatment urinary protein profiling. A total of 15 significantly and consistently down-regulated protein candidates were identified. Among them, alpha-1-antichymotrypsin precursor (AACT), tumor rejection antigen gp96 (GP96) and Zn-Alpha-2-Glycoprotein (ZAG) were selected for further analysis. The results indicated that Western Blot assay of AACT, GP96 and ZAG had advanced the diagnosis time of acute renal rejection by 3 days, compared with current standard clinical observation and laboratory examination. Furthermore, the double-blind detection revealed that the accuracy, sensitivity and specificity of the diagnosis of acute renal rejection of AACT, GP96 and ZAG were 66.67%/100%/60%, 83.33%/100%/80% and 66.67%/100%/60%, respectively, and 100%/100%/100% in combination. In conclusion, urinary protein AACT, GP96 and ZAG could be a set of potential biomarkers for early non-invasive diagnosis of the acute rejection after renal transplantation. [source] REVIEW ARTICLE: The Role of Placental Exosomes in ReproductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Lucia Mincheva-Nilsson Citation Mincheva-Nilsson L, Baranov V. The Role of Placental Exosomes in Reproduction. Am J Reprod Immunol 2010 Cell communication comprises cell,cell contact, soluble mediators and intercellular nanotubes. There is, however, another cell,cell communication by released membrane-bound microvesicles that convey cell,cell contact ,by proxy' transporting signals/packages of information from donor to recipient cells locally and/or at a distance. The nanosized exosomes comprise a specialized type of microvesicles generated within multivesicular bodies (MVB) and released upon MVB fusion with the plasma membrane. Exosomes are produced by a variety of immune, epithelial and tumor cells. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram their recipient cells. Recently, it was discovered that the syncytiotrophoblast constitutively and throughout the pregnancy secretes exosomes. The placenta-derived exosomes are immunosuppressive and carry proteins and RNA molecules that in a redundant way influence a number of mechanisms and promote the fetal allograft survival. In this review, we summarize the current knowledge on the nature of placenta-derived exosomes and discuss their role in pregnancy. [source] In Vivo Function of Immune Inhibitory Molecule B7-H4 in Alloimmune ResponsesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010K. Yamaura B7 ligands deliver both costimulatory and coinhibitory signals to the CD28 family of receptors on T lymphocytes, the balance between which determines the ultimate immune response. Although B7-H4, a recently discovered member of the B7 family, is known to negatively regulate T cell immunity in autoimmunity and cancer, its role in solid organ allograft rejection and tolerance has not been established. Targeting the B7-H4 molecule by a blocking antibody or use of B7-H4,/, mice as recipients of fully MHC-mismatched cardiac allografts did not affect graft survival. However, B7-H4 blockade resulted in accelerated allograft rejection in CD28-deficient recipients. B7-1/B7-2-double-deficient recipients are truly independent of CD28/CTLA-4:B7 signals and usually accept MHC-mismatched heart allografts. Blockade of B7-H4 in these mice also precipitated rejection, demonstrating regulatory function of this molecule independent of an intact CD28/CTLA-4:B7 costimulatory pathway. Accelerated allograft rejection was always accompanied by increased frequencies of alloreactive IFN-,-, IL-4- and Granzyme B-producing splenocytes. Finally, intact recipient, but not donor, B7-H4 is essential for prolongation of allograft survival by blocking CD28/CTLA4:B7 pathway using CTLA4-Ig. These data are the first to provide evidence of the regulatory effects of B7-H4 in alloimmune responses in a murine model of solid organ transplantation. [source] An Early Regional Experience with Expansion of Milan Criteria for Liver Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010J. J. Guiteau The Milan Criteria (MC) showed that orthotopic liver transplantation (OLT) was an effective treatment for patients with nonresectable, nonmetastatic HCC. There is growing evidence that expanding the MC does not adversely affect patient or allograft survival following OLT. The adult OLT programs in UNOS Region 4 reached an agreement allowing lesions outside MC (one lesion <6 cm, ,3 lesions, none >5 cm and total diameter <9 cm,[R4 T3]) to receive the same exception points as MC lesions. Kaplan,Meier curves and log-rank tests were used to compare survival data. Chi-squared and Mann,Whitney U tests were used to compare patient data. A p - value of <0.05 was considered significant. All statistical analyses were performed on SPSS 15 (SPSS, Chicago, IL). Four hundred and forty-five patients were transplanted for HCC (363-MC and 82-R4 T3). Patient demographics were found to be similar between the two groups. Three year patient, allograft and recurrence free survival between MC and R4 T3 were found to be 72.9% and 77.1%, 71% and 70.2% and 90.5% and 86.9%, respectively (all p > 0.05). We report the first regionalized multicenter, prospective study showing benefit of OLT in patients exceeding MC based on preoperative imaging. [source] Islet Transplantation in Type 1 Diabetics Using an Immunosuppressive Protocol Based on the Anti-LFA-1 Antibody EfalizumabAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010A. M. Posselt The applicability of islet transplantation as treatment for type 1 diabetes is limited by renal and islet toxicities of currently available immunosuppressants. We describe a novel immunosuppressive regimen using the antileukocyte functional antigen-1 antibody efalizumab which permits long-term islet allograft survival while reducing the need for corticosteroids and calcineurin inhibitors (CNI). Eight patients with type 1 diabetes and hypoglycemic unawareness received intraportal allogeneic islet transplants. Immunosuppression consisted of antithymocyte globulin induction followed by maintenance with efalizumab and sirolimus or mycophenolate. When efalizumab was withdrawn from the market in mid 2009, all patients were transitioned to regimens consisting of mycophenolate and sirolimus or mycophenolate and tacrolimus. All patients achieved insulin independence and four out of eight patients became independent after single-islet transplants. Insulin independent patients had no further hypoglycemic events, hemoglobin A1c levels decreased and renal function remained stable. Efalizumab was well tolerated and no serious adverse events were encountered. Although long-term follow-up is limited by discontinuation of efalizumab and transition to conventional imunnosuppression (including CNI in four cases), these results demonstrate that insulin independence after islet transplantation can be achieved with a CNI and steroid-free regimen. Such an approach may minimize renal and islet toxicity and thus further improve long-term islet allograft survival. [source] Induction of Indoleamine 2,3-Dioxygenase by Gene Delivery in Allogeneic Islets Prolongs Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010H. Dellê Indoleamine 2,3-dioxygenase (IDO), an enzyme that plays a critical role in fetomaternal tolerance, exerts immunoregulatory functions suppressing T-cell responses. The aims of this study were to promote IDO expression in rat islets using a nonviral gene transfer approach, and to analyze the effect of the in vivo induction of IDO in a model of allogeneic islet transplantation. The IDO cDNA was isolated from rat placenta, subcloned into a plasmid and transfected into rat islets using Lipofectamine. The efficiency of transfection was confirmed by qRT-PCR and functional analysis. The in vivo effect of IDO expression was analyzed in streptozotocin-induced diabetic Lewis rats transplanted with allogeneic islets under the renal capsule. Transplantation of IDO-allogeneic islets reversed diabetes and maintained metabolic control, in contrast to transplantation of allogeneic nontransfected islets, which failed shortly after transplantation in all animals. Graft survival of allograft islets transfected with IDO transplanted without any immunosuppression was superior to that observed in diabetic rats receiving nontransfected islets. These data demonstrated that IDO expression induced in islets by lipofection improved metabolic control of streptozotocin-diabetic rats and prolonged allograft survival. [source] | |||||||||||||||||||||||||