scholarly journals Future of Solid Organ Transplantation: Organ-Specific Tolerance

KIDNEYS ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 130-136
Author(s):  
Yusuf Ercin Sonmez

A transplant between two people who are not genetically identical is called an allotransplant and the process is called allotransplantation. Donor organs and tissues can be from people who are living, or people who have died because of a significant brain injury or lack of circulation. Allotransplantation can create a rejection process where the immune system of the recipient attacks the foreign donor organ or tissue and destroys it. The recipient may need to take immunosuppressive medication for the rest of their life to reduce the risk of rejection of the donated organ. In general, deliberately induced immunosuppression is performed to prevent the body from rejecting an organ transplant. The adverse effects associated with these agents and the risks of long-term immunosuppression present a number of challenges for the clinician. Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in a given organism.

2016 ◽  
Vol 27 (3) ◽  
pp. 316-323
Author(s):  
Michael Petty

Within a little more than a decade, the transplant of human organs for end-stage organ disease became a reality. The early barriers to successful long-term graft and patient survival were related to the inability to effectively control the immune system such that it would not attack the donor tissue but would still recognize and destroy invading organisms and cells. As immunosuppressive therapy has been refined and proper matching of donors and recipients has been improved, hyperacute rejection has become a rare occurrence and acute rejection has been markedly controlled. However, antibody-mediated rejection remains an important impediment to increased survival of transplanted organs. This article provides readers with a broad overview of the immune system, discusses mechanisms of transplant rejection, and details prevention, detection, and treatment of antibody-mediated rejection in solid organ transplant.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kadiyala V. Ravindra ◽  
Hong Xu ◽  
Larry D. Bozulic ◽  
David D. Song ◽  
Suzanne T. Ildstad

Successful hand and face transplantation in the last decade has firmly established the field of vascularized composite allotransplantation (VCA). The experience in VCA has thus far been very similar to solid organ transplantation in terms of the morbidity associated with long-term immunosuppression. The unique immunological features of VCA such as split tolerance and resistance to chronic rejection are being investigated. Simultaneously there has been laboratory work studying tolerogenic protocols in animal VCA models. In order to optimize VCA outcomes, translational studies are needed to develop less toxic immunosuppression and possibly achieve donor-specific tolerance. This article reviews the immunology, animal models, mixed chimerism & tolerance induction in VCA and the direction of future research to enable better understanding and wider application of VCA.


2016 ◽  
Vol 1 (1) ◽  
pp. 12
Author(s):  
Hans-Dieter Volk ◽  
Bernhard Banas ◽  
Frederike Bemelman ◽  
Oriol Bestard ◽  
Sophie Brouard ◽  
...  

Solid organ transplantation has emerged as the “gold standard” therapy for end-stage organ failure as it improves both quality of life and survival. Despite the progress in short-term graft survival, that is closely associated with the impressive reduction of acute rejections within the first year, long-term graft and patient survival remain almost un-changed and unsatisfactory. Incomplete control of chronic allograft injury but particularly the adverse effects of long-term immunosuppression, such as graft toxicity, diabetes, cardiovascular events, infections, and tumours continue to challenge the long-term success. In general, immunosuppression is applied as one-size-fits-all strategy. This can result in over- and under-immunosuppression of patients with low and high alloresponsiveness, respectively. Trial- and -error strategies to minimize or even completely wean of immunosuppression have a high failure rate. Consequently, there is an unmet medical need to develop biomarkers allowing objective risk stratification of transplant patients. To achieve this goal, we engaged in an academic-industrial partnership. The central focus of the European-wide BIO-DrIM consortium (BIOmarker-Driven IMmmunosuppression) is the implementation of biomarker-guided strategies for personalizing immunosuppression to improve the long-term outcome and to decrease the adverse effects and costs of chronic immunosuppression in solid organ transplant patients. The concept includes four innovative investigator-driven clinical trials designed by the consortium.


2020 ◽  
Vol 26 (28) ◽  
pp. 3497-3506
Author(s):  
Raymund R. Razonable

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.


2021 ◽  
Vol 28 (1) ◽  
pp. 661-670
Author(s):  
Lawrence Kasherman ◽  
Jeffrey Doi ◽  
Katherine Karakasis ◽  
Jeffrey Schiff ◽  
Abhijat Kitchlu ◽  
...  

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.


2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S1-S1
Author(s):  
T Kitano ◽  
M Science ◽  
N Nalli ◽  
K Timberlake ◽  
U Allen ◽  
...  

Abstract Background Solid-organ transplant (SOT) patients are more vulnerable to infections by antimicrobial-resistant organisms (AROs) because of their hospital exposure, compromised immune systems, and antimicrobial exposure. Therefore, it may be useful for transplant facilities to create transplant-specific antibiograms to direct empirical antimicrobial regimens and monitor trends in antimicrobial resistance. Methods SOT (i.e., lung, liver, renal, and heart) antibiograms were created using antimicrobial susceptibility data on isolates from 2012 to 2018 at The Hospital for Sick Children, a tertiary pediatric hospital and transplant center in Toronto, Ontario. The Clinical Laboratory Standards Institute (CLSI) guidelines were followed to generate the antibiograms. The first clinical isolate of a species from a patient in each year was included irrespective of body site; duplicates were eliminated and surveillance cultures were excluded. Results from 2 years of data were pooled on a rolling basis to achieve an adequate sample size in both SOT and hospital-wide antibiogram. The SOT antibiogram was then compared with the hospital-wide antibiogram of the compatible 2 pooled years from 2012 to 2018. For subgroup analyses in the SOT population, organ-specific antibiograms and transplant timing-specific antibiograms (pretransplant, post-transplant <1 year, and post-transplant ≥1 year) between transplant and sample collection dates were analyzed. All proportions were compared using the χ 2 test. Results The top 5 organisms in one (2 year) analysis period of the SOT antibiogram were Escherichia coli (n = 29), Staphylococcus aureus (n = 28), Pseudomonas aeruginosa (n = 20), Enterobacter cloacae complex (n = 18), and Klebsiella pneumoniae (n = 17). For E.coli, susceptibility in the SOT antibiogram was significantly lower than those in the hospital-wide antibiogram in 2017/2018 for ampicillin (27% vs. 48%; P = 0.015), piperacillin/tazobactam (55% vs. 87%; P < 0.001), cefotaxime (59% vs. 88%; P < 0.001), ciprofloxacin (71% vs. 87%; P = 0.007) and cotrimoxazole (41% vs. 69%; P < 0.001), but not significantly different for gentamicin (94% vs. 91%; P = 0.490), tobramycin (88% vs. 90%; P = 0.701) and amikacin (100% vs. 99%; P = 0.558). These findings were consistent throughout the study period in E.coli. There was no statistically significant difference between the SOT and hospital-wide antibiograms for other organisms. There were no significant differences in susceptibility between organ-specific antibiograms or transplant timing-specific antibiograms in 2012–2018. Conclusions We found that E.coli from the SOT population had a significantly lower sensitivity to all antimicrobials, except aminoglycosides, compared with those from the hospital-wide population. Other organisms had similar susceptibility to the hospital-wide population. Developing a SOT antibiogram will assist in revising and improving empiric treatment guidelines for this population.


BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043731
Author(s):  
Adnan Sharif ◽  
Javeria Peracha ◽  
David Winter ◽  
Raoul Reulen ◽  
Mike Hawkins

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.


2011 ◽  
Vol 36 (8) ◽  
pp. 891-901 ◽  
Author(s):  
Katie A. Devine ◽  
Bonney Reed-Knight ◽  
Kristin A. Loiselle ◽  
Laura E. Simons ◽  
Laura L. Mee ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Reuben J. Arasaratnam ◽  
Alejandro Restrepo

Posttransplant lymphoproliferative disease is a serious complication following stem cell and solid organ transplantation. Early recognition of the disease is important in facilitating timely therapy and improving long-term outcomes. We report a renal transplant recipient presenting with an extracranial frontoparietal soft tissue mass that was subsequently diagnosed as a B-cell lymphoma. The patient was treated successfully with immunosuppression reduction, anti-CD20 monoclonal antibody therapy, and cytotoxic chemotherapy. Our case highlights the importance of recognizing soft tissue masses in the head and neck as a potential clinical manifestation of PTLD in solid organ transplant recipients.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S636-S636
Author(s):  
Kyla L Naylor ◽  
Alexandra Ouédraogo ◽  
Sarah E Bota ◽  
Shahid Husain ◽  
J Michael Paterson ◽  
...  

Abstract Background Invasive fungal infection (IFI) in solid-organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long-term probability of post-transplant IFI is poorly understood. Methods We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada to determine the incidence rate, 1-, 5- and 10-year cumulative probability of IFI-related hospitalization, and 1-year post-IFI all-cause mortality in SOT recipients from 2002 to 2016. We also examined post-IFI death-censored graft failure in renal transplant patients. Results We included 9326 SOT recipients (median follow-up 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person-years (95% confidence interval [CI]: 7.5–9.1). The 1-year cumulative probability of IFI was 7.4% (95% CI: 5.8–9.3%), 5.4% (95% CI: 3.6–8.1%), 1.8% (95% CI: 1.3–2.5%), 1.2% (95% CI: 0.5–3.2%), and 1.1% (95% CI: 0.9–1.4%) for lung, heart, liver, kidney-pancreas, and kidney-only transplant recipients, respectively. Lung transplant recipients had both the highest incidence rate and the highest 10-year probability of IFI: 43.0 per 1,000 person-years (95% CI: 36.8–50.0) and 26.4% (95% CI: 22.4–30.9%), respectively. Lung transplantation was also associated with the highest 1-year cumulative probability of post-IFI all-cause mortality (40.2%,95% CI: 33.1–48.3%). Among kidney transplant recipients, the 1-year probability of death-censored graft failure after IFI was 9.8% (95% CI: 6.0–15.8%). Conclusion The 1-year cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1-year all-cause mortality. The findings of this study considerably improved our understanding of the long-term probability of post-transplant IFI. Disclosures All authors: No reported disclosures.


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