scholarly journals The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?

2021 ◽  
Vol 12 ◽  
Author(s):  
Mepur H. Ravindranath ◽  
Fatiha El Hilali ◽  
Edward J. Filippone
Keyword(s):  
Immune Responses ◽  
Inflammatory Mediators ◽  
Solid Organ Transplantation ◽  
Reciprocal Relationship ◽  
Solid Organ ◽  
Cell Surface Antigens ◽  
Passenger Leukocytes ◽  
Cross Dressing ◽  
Allograft Loss ◽  
The Impact

Transplantation (Tx) remains the optimal therapy for end-stage disease (ESD) of various solid organs. Although alloimmune events remain the leading cause of long-term allograft loss, many patients develop innate and adaptive immune responses leading to graft tolerance. The focus of this review is to provide an overview of selected aspects of the effects of inflammation on this delicate balance following solid organ transplantation. Initially, we discuss the inflammatory mediators detectable in an ESD patient. Then, the specific inflammatory mediators found post-Tx are elucidated. We examine the reciprocal relationship between donor-derived passenger leukocytes (PLs) and those of the recipient, with additional emphasis on extracellular vesicles, specifically exosomes, and we examine their role in determining the balance between tolerance and rejection. The concept of recipient antigen-presenting cell “cross-dressing” by donor exosomes is detailed. Immunological consequences of the changes undergone by cell surface antigens, including HLA molecules in donor and host immune cells activated by proinflammatory cytokines, are examined. Inflammation-mediated donor endothelial cell (EC) activation is discussed along with the effect of donor-recipient EC chimerism. Finally, as an example of a specific inflammatory mediator, a detailed analysis is provided on the dynamic role of Interleukin-6 (IL-6) and its receptor post-Tx, especially given the potential for therapeutic interdiction of this axis with monoclonal antibodies. We aim to provide a holistic as well as a reductionist perspective of the inflammation-impacted immune events that precede and follow Tx. The objective is to differentiate tolerogenic inflammation from that enhancing rejection, for potential therapeutic modifications. (Words 247).

scholarly journals COVID‐19 in solid organ transplantation: an analysis of the impact on transplant activity and wait lists

2020 ◽  
Vol 34 (1) ◽  
pp. 209-212
Author(s):  
Maria Irene Bellini ◽  
Francesco Tortorici ◽  
Marco Capogni
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
The Impact

scholarly journals Modulation of immune responses following solid organ transplantation by microRNA

2012 ◽  
Vol 93 (3) ◽  
pp. 378-385 ◽  
Author(s):  
Nayan J. Sarma ◽  
Venkataswarup Tiriveedhi ◽  
Sabarinathan Ramachandran ◽  
Jeffrey Crippin ◽  
William Chapman ◽  
...  
Keyword(s):  
Immune Responses ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ

What Is the Impact of Hypogammaglobulinemia on the Rate of Infections and Survival in Solid Organ Transplantation? A Meta-Analysis

2013 ◽  
Vol 13 (10) ◽  
pp. 2601-2610 ◽  
Author(s):  
D. F. Florescu ◽  
A. C. Kalil ◽  
F. Qiu ◽  
C. M. Schmidt ◽  
U. Sandkovsky
Keyword(s):  
Organ Transplantation ◽  
Meta Analysis ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
The Impact

scholarly journals The Impact of Donor and Recipient Genetic Variation on Outcomes After Solid Organ Transplantation

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Yanni Li ◽  
Lianne M. Nieuwenhuis ◽  
Brendan J. Keating ◽  
Eleonora A.M. Festen ◽  
Vincent E. de Meijer
Keyword(s):  
Genetic Variation ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
The Impact

scholarly journals Heterologous Immunity of Virus-Specific T Cells Leading to Alloreactivity: Possible Implications for Solid Organ Transplantation

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2359
Author(s):  
Gonca E. Karahan ◽  
Frans H. J. Claas ◽  
Sebastiaan Heidt
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Organ Transplantation ◽  
Specific Antigen ◽  
Solid Organ Transplantation ◽  
Adaptive Immune System ◽  
Cross Reactivity ◽  
Solid Organ ◽  
Heterologous Immunity ◽  
Specific Memory

Exposure of the adaptive immune system to a pathogen can result in the activation and expansion of T cells capable of recognizing not only the specific antigen but also different unrelated antigens, a process which is commonly referred to as heterologous immunity. While such cross-reactivity is favourable in amplifying protective immune responses to pathogens, induction of T cell-mediated heterologous immune responses to allo-antigens in the setting of solid organ transplantation can potentially lead to allograft rejection. In this review, we provide an overview of murine and human studies investigating the incidence and functional properties of virus-specific memory T cells cross-reacting with allo-antigens and discuss their potential relevance in the context of solid organ transplantation.

scholarly journals 2697. The Impact of Universal Deceased Donor Screening on Donor-Derived Toxoplasmosis in Solid-Organ Transplant: Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S948-S948
Author(s):  
Lynne Strasfeld ◽  
Ricardo M La Hoz ◽  
Gabe Vece ◽  
Cameron R Wolfe ◽  
Marian G Michaels
Keyword(s):  
Disease Transmission ◽  
Ad Hoc ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Deceased Donor ◽  
Solid Organ ◽  
Serologic Testing ◽  
Deceased Donors ◽  
Optimal Approach ◽  
The Impact

Abstract Background Donor-derived toxoplasmosis (DDT) is a severe and potentially life-threatening infection after solid-organ transplantation (SOT). Serologic testing for Toxoplasma gondii is required for all deceased donors per OPTN policy as of 4/6/17. To assess the impact of universal donor testing and the optimal approach to DDT prevention, we analyzed potential DDT cases reviewed by DTAC. Methods All potential Toxoplasma donor-derived transmission events adjudicated by DTAC from 2008 to 2018 were reviewed. A standardized classification algorithm was used to adjudicate each event as proven, probable, possible, unlikely, excluded or intervention without disease transmission. Results Twenty-eight potential DDT events were reported between 2008 and 2018. Proven or probable (p/p) DDT developed in 16 organ recipients from 15 donors. In the 9 years prior to the new testing requirement (January 2008–March 2017) 11 organ recipients from 10 donors had p/p DDT (0.13 transmissions per 1,000 donors); in the first 21 months of the new testing requirement 5 recipients from 5 donors had p/p DDT (0.27 transmissions per 1,000 donors), rate ratio 2.15; 95% CI 0.577, 6.90;P = 0.18. 10.2% of 18,328 donors tested between April 6, 2017 and December 31, 2018 were Toxoplasma IgG seropositive. Recipient pre-SOT serostatus was unknown in 4 of 5 and negative in 1 case of p/p DDT. Trimethoprim/sulfamethoxazole prophylaxis was either stopped at < 3 months or not used in all 5 cases. Infection was diagnosed a median of 103 days (range 42–153) post-transplant. Four of the 5 recipients died. Conclusion DDT remains a morbid infection in both heart and non-heart recipients. Despite an apparent increase in DDT reporting to DTAC, it is unlikely that the actual incidence of this donor-derived event is increasing. Rather, with universal serologic screening of deceased donors and wider access to molecular diagnostics, DDT is increasingly recognized and diagnosed. To decrease risk for illness and death related to DDT, broader pre-transplant recipient serologic testing and use of prophylaxis or monitoring for high-risk serostatus recipients (Toxoplasma D+/R−) is critical. The optimal duration of prophylaxis is uncertain at this time and warrants further study. Disclosures All authors: No reported disclosures.

scholarly journals Multicenter Analysis of 80 Solid Organ Transplantation Recipients With Post-Transplantation Lymphoproliferative Disease: Outcomes and Prognostic Factors in the Modern Era

2010 ◽  
Vol 28 (6) ◽  
pp. 1038-1046 ◽  
Author(s):  
Andrew M. Evens ◽  
Kevin A. David ◽  
Irene Helenowski ◽  
Beverly Nelson ◽  
Dixon Kaufman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Organ Transplantation ◽  
Bone Marrow Involvement ◽  
Solid Organ Transplantation ◽  
Progression Free Survival ◽  
Lymphoproliferative Disease ◽  
Solid Organ ◽  
Post Transplantation ◽  
Cart Analysis ◽  
The Impact

Purpose Adult post-transplantation lymphoproliferative disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) –related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, ≥ 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P < .0001). Conclusion This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.

Gastrointestinal Side Effects of Post-Transplant Therapy

2016 ◽  
Vol 25 (3) ◽  
pp. 367-373 ◽  
Author(s):  
Valerian Ciprian Lucan ◽  
Luisa Berardinelli
Keyword(s):  
Side Effects ◽  
Immunosuppressive Therapy ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Post Transplant ◽  
Medication Side ◽  
Gastrointestinal Side Effects ◽  
Inflammatory Drugs ◽  
The Impact

Modern immunosuppressive therapy has produced a real revolution in renal and organ transplantation but it comes with the price of multiple side effects. There are many gastrointestinal (GI) complications that are the consequence of transplant immunosuppressant medication. In fact, for any immunosuppressant therapy, certain standardized precepts and attitudes that aim to reduce the incidence and the impact of the medication side effects must be applied. Many patients undergo renal transplantation and the physicians have to be aware of the advantages and the risks associated. This article reviews the main GI complications that may arise as a consequence of immunosuppressive therapy after solid organ transplantation, focusing on renal and renal/pancreas transplantation, as well as the ways in which the incidence of these complications can be reduced. Management of the post-transplant therapy is mandatory in order to increase not only the grafts’ and the patients’ survival, but also their quality of life by the occurrence of fewer complications. Abbreviations: Aza: azathioprine; CMV: cytomegalovirus; CsA: cyclosporine A; GI: gastrointestinal; MMF: mycophenolate mofetil; NSAID: non-steroidal anti-inflammatory drugs; Tac: tacrolimus.

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