Induction of allograft tolerance through costimulatory blockade: first selection of drugs in vitro

Vierboom, Michel; Ossevoort, Miriam; Sick, Ella A.; Haanstra, Krista G.; Jonker, Margreet

doi:10.1016/s0966-3274(03)00009-1

Cited by 14 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The most striking alteration is found in phenotypes and functions of T cell and less frequently in components of the natural (innate) immune system with relative preservation of complement activity, chemotaxis, phagocytosis, and natural cytotoxicity [17]. The co-stimulatory pathway of allorecognition, which is critical in T-cell activation, is of paramount importance in transplant rejection, and tolerance is impaired in elderly individuals [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Renal transplantation in the elderly: South Indian experience

et al. 2011

View full text Add to dashboard Cite

In developing countries, renal transplantation is offered to young end-stage renal disease (ESRD) patients, while the older ones face limitations due to higher mortality risk. We retrospectively analyzed 225 patients who underwent renal transplantation from living donors, aged 40-60 years (Group A) and >60 years (Group B), focusing on their survival outcome. Group A (n = 181) had mean creatinine (mg/dL) 1.41 ± 0.84, 1.30 ± 0.65 and 1.40 ± 0.60 and mean eGFR (mL/min/1.73 m(2)) of 65.32 ± 23.03, 69.14 ± 32.65 and 59.21 ± 22.79 at 0, 3 and 6 months post-transplantation. Death-censored graft survival was 93.1% in first year followed by 91.2% in subsequent 4 years. Patient survival was 92.5% in first year, 90.7% in the next 2 years, and 89.2% in 4th year. Highest cumulative graft survival was 86.7% in the first year with 83.4%, 82.7% and 82.4% during the subsequent 3 years. Group B (n = 44) had mean creatinine (mg/dL) of 1.46 ± 1.02, 1.29 ± 0.23 and 1.2 ± 0.29 with a mean eGFR (mL/min/1.73 m(2)) of 67.90 ± 23.48, 67.02 ± 12.76 and 75.23 ± 15.19 at 0, 3 and 6 months. Highest death-censored graft survival was 97.4% in the first year with 94.7% in next 3 years. Patient survival was 88.1% throughout 4 years post-transplantation. Cumulative graft survival was 84.1% during 4 years. Biopsy-proven acute rejection rate was 28.7% in group A and 15.9% in group B (P = 0.058). There was higher mortality rate in group B with death mainly due to infections and cardiovascular complication. Cardiovascular risk assessment, pre-transplant cancer screening and judicious use of immunosuppressive agents should help minimize adverse events, balanced with an inherently reduced risk of acute rejection, hence the graft survival advantage and is the way forward to maximize patient and renal allograft survival in elderly patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Renal transplantation in the elderly: South Indian experience

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The most striking alterations are found in phenotypes and functions of T-cell components and less frequently in components of the natural (innate) immune system with relative preservation of complement activity, chemotaxis, phagocytosis, and natural cytotoxicity [50]. The costimulatory pathways of allorecognition, which are critical in T-cell activation and have paramount importance in transplant rejection and tolerance, are, however, impaired in elderly individuals [51][52][53]. Age-related changes of the immune system have impact both on the elderly recipient and on the aged graft.…”

Section: Impact Of Recipient Age On Transplant Outcomesmentioning

confidence: 99%

Renal transplantation in the elderly

Saxena

Yu²,

Giraldo

et al. 2008

Int Urol Nephrol

View full text Add to dashboard Cite

Elderly patients are increasingly being considered for kidney transplantation due to a global explosion of the aging population with end-stage renal disease (ESRD). However, mounting scarcity of available organs for transplant has led to a wider disparity between organ supply and demand. Consequently, the criteria for accepting kidneys for transplantation have been extended in an attempt to allow the use of organs from elderly donors or those with significant co-morbidities, so-called "expanded criteria donor" (ECD) kidneys. Excellent outcomes have been achieved from ECD kidneys with appropriate donor and recipient profiling and selection. With increasing recovery efforts directed at older donors, the concept of age-matching is becoming more accepted as a method of optimizing utilization of organs in elderly donors and recipients. Utilization of pulsatile perfusion has further improved ECD outcomes and helped the decision-making process for the UNOS (United Network for Organ Sharing) offer. However, age-related immune dysfunction and associated co-morbidities make the elderly transplant recipients ever more susceptible to complications associated with immunosuppressive agents. Consequently, the elderly population is at a higher risk to develop infections and malignancy in the post-transplant period notwithstanding improved transplant outcomes. Appropriate immunosuppressive agents and dosages should be selected to minimize adverse events while reducing the risk of acute rejections and maximizing patient and renal allograft survival.

show abstract

“…The focus in CFIT on interference with immune activation/tolerance is evidenced by references (28, 32–36) and the focus on somatic gene therapy/stem cells by (29–31). The development and improvement of non-invasive methods has resulted in three additional publications (20, 56, 57). The focus of the PCDD program on tolerance induction is unfortunately not reflected in publications, illustrating the already mentioned difficulty in tolerance induction in the pathogen-educated primate immune system.…”

Section: Achievementsmentioning

confidence: 99%

An Evaluation of 20 Years of EU Framework Programme-Funded Immune-Mediated Inflammatory Translational Research in Non-Human Primates

2016

View full text Add to dashboard Cite

Aging western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which often no effective treatments exist, resulting in increasing health-care expenditure. Despite high investments in drug development, the number of promising new drug candidates decreases. We propose that preclinical research in non-human primates can help to bridge the gap between drug discovery and drug prescription. Translational research covers various stages of drug development of which preclinical efficacy tests in valid animal models is usually the last stage. Preclinical research in non-human primates may be essential in the evaluation of new drugs or therapies when a relevant rodent model is not available. Non-human primate models for life-threatening or severely debilitating diseases in humans are available at the Biomedical Primate Research Centre (BPRC). These have been instrumental in translational research for several decades. In order to stimulate European health research and innovation from bench to bedside, the European Commission has invested heavily in access to non-human primate research for more than 20 years. BPRC has hosted European users in a series of transnational access programs covering a wide range of research areas with the common theme being immune-mediated inflammatory disorders. We present an overview of the results and give an account of the studies performed as part of European Union Framework Programme (EU FP)-funded translational non-human primate research performed at the BPRC. These data illustrate the value of translational non-human primate research for the development of new therapies and emphasize the importance of EU FP funding in drug development.

show abstract

Induction of allograft tolerance through costimulatory blockade: first selection of drugs in vitro

Cited by 14 publications

References 33 publications

Renal transplantation in the elderly: South Indian experience

Renal transplantation in the elderly: South Indian experience

Renal transplantation in the elderly

An Evaluation of 20 Years of EU Framework Programme-Funded Immune-Mediated Inflammatory Translational Research in Non-Human Primates

Contact Info

Product

Resources

About