Hand Transplantation: The State-of-the-Art

2007 ◽  
Vol 32 (1) ◽  
pp. 2-17 ◽  
Author(s):  
F. SCHUIND ◽  
D. ABRAMOWICZ ◽  
S. SCHNEEBERGER
Keyword(s):  
State Of The Art ◽  
Therapeutic Option ◽  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Psychological Status ◽  
Solid Organ ◽  
Psychological Benefits ◽  
Hand Transplantation ◽  
Key Issues ◽  
Specific Tolerance

The feasibility of hand transplantation has been demonstrated, both surgically and immunologically. Levels of immunosuppression comparable to regimens used in solid organ transplantation are proving sufficient to prevent graft loss. Many patients have achieved discriminative sensibility and recovery of intrinsic muscle function. In addition to restoration of function, hand transplantation offers considerable psychological benefits. The recipient’s pre-operative psychological status, his motivation and his compliance with the intense rehabilitation programme are key issues. While the induction of graft specific tolerance represents a hope for the future, immunosuppression currently remains necessary and carries significant risks. Hand transplantation should, therefore, only be considered a therapeutic option for a carefully selected group of patients.

scholarly journals Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art

2021 ◽  
Vol 7 (6) ◽  
pp. 451
Author(s):  
Georgios Karavalakis ◽  
Evangelia Yannaki ◽  
Anastasia Papadopoulou
Keyword(s):  
Host Defense ◽  
Hematopoietic Cell Transplantation ◽  
State Of The Art ◽  
Fungal Infections ◽  
Solid Organ Transplantation ◽  
Immunocompromised Host ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Cell Immunotherapy ◽  
Life Threatening

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

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

KIDNEYS ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 130-136
Author(s):  
Yusuf Ercin Sonmez
Keyword(s):  
Immune System ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Immunological Tolerance ◽  
The Body ◽  
Solid Organ ◽  
Donor Organ ◽  
Organ Specific ◽  
Specific Tolerance

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.

scholarly journals Epitope-Level Matching—A Review of the Novel Concept of Eplets in Transplant Histocompatibility

2021 ◽  
Vol 2 (3) ◽  
pp. 336-347
Author(s):  
André Renaldo ◽  
Adriel Roa-Bautista ◽  
Elena González-López ◽  
Marcos López-Hoyos ◽  
David San Segundo
Keyword(s):  
De Novo ◽  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Human Leukocyte ◽  
Future Research ◽  
Solid Organ ◽  
Leukocyte Antigen ◽  
Definition Of ◽  
Novel Concept ◽  
Hla Compatibility

The development of de novo donor-specific antibodies is related to the poor matching of the human leukocyte antigen (HLA) between donor and recipient, which leads to dismal clinical outcomes and graft loss. However, new approaches that stratify the risks of long-term graft failure in solid organ transplantation have emerged, changing the paradigm of HLA compatibility. In addition, advances in software development have given rise to a new structurally based algorithm known as HLA Matchmaker, which determines compatibility at the epitope rather than the antigen level. Although this technique still has limitations, plenty of research maintains that this assessment represents a more complete and detailed definition of HLA compatibility. This review summarizes recent aspects of eplet mismatches, highlighting the most recent advances and future research directions.

scholarly journals M2 Macrophages Serve as Critical Executor of Innate Immunity in Chronic Allograft Rejection

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanwen Zhang ◽  
Zhuonan Li ◽  
Wei Li
Keyword(s):  
Allograft Rejection ◽  
Chronic Rejection ◽  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Innate Immune ◽  
Sterile Inflammation ◽  
Solid Organ ◽  
M2 Macrophages ◽  
Innovative Strategies ◽  
Chronic Allograft Rejection

Allograft functional failure due to acute or chronic rejection has long been a major concern in the area of solid organ transplantation for decades. As critical component of innate immune system, the macrophages are unlikely to be exclusive for driving acute or chronic sterile inflammation against allografts. Traditionally, macrophages are classified into two types, M1 and M2 like macrophages, based on their functions. M1 macrophages are involved in acute rejection for triggering sterile inflammation thus lead to tissue damage and poor allograft survival, while M2 macrophages represent contradictory features, playing pivotal roles in both anti-inflammation and development of graft fibrosis and resulting in chronic rejection. Macrophages also contribute to allograft vasculopathy, but the phenotypes remain to be identified. Moreover, increasing evidences are challenging traditional identification and classification of macrophage in various diseases. Better understanding the role of macrophage in chronic rejection is fundamental to developing innovative strategies for preventing late graft loss. In this review, we will update the recent progress in our understanding of diversity of macrophage-dominated innate immune response, and reveal the roles of M2 macrophages in chronic allograft rejection as well.

Anti-CD20 Monoclonal Antibody (rituximab) for Refractory PTLD after Pediatric Solid Organ Transplantation: Multicenter Experience from a Registry and from a Prospective Clinical Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 746-746 ◽  
Author(s):  
Steven Webber ◽  
William Harmon ◽  
Albert Faro ◽  
Michael Green ◽  
Minnie Sarwal ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Monoclonal Antibody ◽  
B Cell ◽  
Organ Transplantation ◽  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Refractory Disease ◽  
First Line

Abstract Background: Anti B cell antibodies have been proposed as a treatment for post-transplant lymphoproliferative disorders (PTLD). Experience in children is limited. Methods and Results: We report experience (n=40) with use of the chimeric mouse/human antiCD20 monoclonal antibody (rituximab) in pediatric PTLD patients with refractory disease (no response to reduced immunosuppression, progressive or relapsed disease, or concomitant allograft rejection). Initial experience was through a voluntary registry (n=26), and most recent experience is from an onging prospective, non-randomized clinical trial (n=14). Use of chemotherapy or other experimental therapies were an exclusion criteria for both studies. All PTLD were of B cell origin and expressed CD20 and all but 2 (both in registry cohort) were EBV positive. The first cohort (registry) comprised 26 solid organ recipients from 12 centers (heart 11, kidney 6, lung 4, other 5) with mean age of 12.5 years, 29 months (range 2–132) from transplant. Histology revealed these lesions: polymorphic 17, monomorphic 7 (including 1 Burkitts-like), Hodgkins-like 1, unspecified 1. 21/26 received 375mg/m2 x 4 doses. There were no SAE’s. 18 pts (69%) showed CR, and 4 (16%) showed PR. The 4 non-responders comprised the 2 EBV negative cases, the Burkitts-like disease and the earliest onset case (fulminant disease at 2 months post-transplant). At latest follow-up (mean 41 months), 73% survive with one graft loss (kidney). In the prospective clinical trial, 14 patients (to date) with refractory disease were enrolled. The protocol comprises 4 doses of 375mg/m2 (weeks 1–4) with no further treatment for patients with CR or for those with no response. Patients with PR receive 4 further doses (weeks 5–8). The 14 patients were from 5 centers (lung 5, kidney 5, heart 4) with mean age of 6.5 years, 41 months (range 4–120) from transplant. Histology revealed the following: polymorphic 10, monomorphic 3, Hodgkin-like 1. There were no SAE’s. Two are still recieving therapy. Of the other 12, 9 (75%) acheived CR and 10 pts (83%) are alive with one graft loss (kidney) at mean follow-up of 1.5 years. The two deaths were due to fungal pneumonia and complications of elective surgery in a patient in CR (both lung recipients). Conclusions: These results suggest that rituximab may have an important role to play in management of refractory PTLD in solid organ recipients (CR rate approx. 70–75% with low incidence of graft loss). This group of patients traditionally has high mortality and has been treated with chemotherapy. Rituximab should be considered as first line treatment for refractory polymorphic PTLD in children after solid organ transplantation. Role in monomorphic disease requires further investigation. Use of rituximab as first line therapy is under investigation.

scholarly journals New-Onset Diabetes after Transplant (NODAT)

2015 ◽  
Vol 12 (4) ◽  
pp. 301-305 ◽  
Author(s):  
R Maskey
Keyword(s):  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Onset Diabetes ◽  
Definition Of ◽  
Liver Transplant Recipients ◽  
New Onset

New onset diabetes mellitus after transplantation (NODAT) is a well known complication following solid organ transplantation and has been reported to occur in 4% to 25% of renal transplant recipients, 2.5% to 25% of liver transplant recipients, hepatitis C virus (HCV) infection between 40% and 60% and 2% to 53% of all solid organ transplants. This variation in the reported incidence may be because of lack of a universal agreement on the definition of NODAT, the duration of follow-up, and the presence of modifiable and non-modifiable risks factors. Moreover, reduced patient survival and accelerated graft loss have been reported with NODAT. In our country also there is increasing in number of kidney transplants patients and along with that there is chance of development of NODA. It is better to detect the NODATS early. So in this article I tried to presents an overview of the literature on the current diagnostic criteria for NODAT and discuss suggested risk factors for the development of NODAT, its potential pathogenic mechanisms, and its impact on post-transplant outcomes after solid organ transplantation.Kathmandu University Medical Journal Vol.12(4) 2014; 301-305

Chronic graft loss: dealing with the vascular alterations in solid organ transplantation

1998 ◽  
Vol 30 (5) ◽  
pp. 2413-2418 ◽  
Author(s):  
N.S Cook ◽  
H.-G Zerwes ◽  
M Rudin ◽  
N Beckmann ◽  
H.-J Schuurman
Keyword(s):  
Organ Transplantation ◽  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Solid Organ

HLA-B7 β-pleated sheet-derived synthetic peptides are immunodominant T-cell epitopes regulating alloresponses

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3286-3292 ◽  
Author(s):  
Anja Freese ◽  
Nicholas Zavazava
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Rejection ◽  
Graft Loss ◽  
Peptide Binding ◽  
Solid Organ Transplantation ◽  
Target Cells ◽  
Solid Organ ◽  
T Cell Epitopes ◽  
Pleated Sheet

Abstract Chronic rejection of transplanted allografts is the major cause of graft loss after clinical solid organ transplantation. Recent data link the indirect presentation of allopeptides to chronic graft loss; thus, identification of immunodominant epitopes on major histocompatibility complex (MHC) antigens could significantly contribute to establishing novel ways for monitoring and managing chronic rejection. Here, we show that synthetic allo-MHC–derived peptides covering the polymorphic region 56 to120 of HLA-B7 modulate alloresponses. In particular, the 2 β-pleated sheet-derived peptides covering residues 91 to 105 and 96 to 120, respectively, but not sequences from the α1 helix, were presented by autologous peripheral blood lymphocytes to induce T-cell proliferation. In addition, the 2 β-pleated sheet-derived peptides and the α1-derived peptide residues 60 to 75 abrogated lysis of HLA-B7 target cells by anti–HLA-B7 cytotoxic T lymphocytes (CTLs). Although most residues between 91 and 120 are normally not directly accessible to T cells, our results indicate that peptides derived from the lower surface of the peptide-binding groove of HLA-B7 are immunodominant in HLA-B7 alloresponses. To characterize the binding and stability of allopeptides to T cells, the 62-70 peptide—derived from the 60-75 allopeptide that blocked cytotoxicity of anti–HLA-B7 CTL—was synthesized and coupled with fluorescein isothiocyanate. The peptide specifically labeled anti-B7 CTL, but not anti–HLA-A2 CTL as measured by flow cytometry. Peptide binding to CTL was specific at 4°C and remained stable for 12 hours, whereas it remained stable for less than 2 hours at 37°C. These studies allow the identification of HLA-B7 T-cell epitopes and reveal for the first time a novel, previously unrecognized application of synthetic HLA-derived allopeptides to visualize alloreactive T cells.

#18: Brincidofovir for the Treatment of Disseminated Human Adenovirus Infection in Pediatric Solid-organ Transplant Recipients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S3-S3
Author(s):  
Jackson Londeree ◽  
Rouba Garro ◽  
Rene Romero ◽  
Roshan George ◽  
Pamela Winterberg ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Severe Disease ◽  
Treatment Options ◽  
Graft Loss ◽  
Clinical Specimen ◽  
Antiviral Drug ◽  
Solid Organ Transplantation ◽  
Kidney Injury ◽  
Human Adenovirus ◽  
Solid Organ

Abstract Background Human adenovirus (HAdV) viremia can cause significant morbidity among pediatric patients undergoing solid-organ transplantation (SOT). Currently, there are no US Food and Drug Administration (FDA)-approved treatments for HAdV infections, and historically the mainstay of treatment has been decreasing immunosuppression with antiviral therapies reserved for those with severe disease. Brincidofovir (BCV) is an investigational antiviral drug with potency against HAdV. We describe four cases of disseminated HAdV infection treated with (BCV) among pediatric SOT patients. Methods We retrospectively reviewed 4 cases of severe disseminated HAdV infection, which occurred between 2018 and 2019, in a tertiary pediatric transplant center. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. Baseline clinical characteristics, disease course, treatment, and outcomes were reviewed. Results Four pediatric SOT patients (2 kidneys, 1 dual kidney/liver, and 1 liver) ranging in age from 9 months to 19 years were diagnosed with HAdV infection (Table 1). Patients presented with varied symptoms from 12 to 912 days post-transplant. Peak HAdV viral load ranged from 37,000 to >1,000,000 copies/mL. All patients had disseminated disease with evidence of graft involvement and varying degrees of acute kidney injury (AKI) making them candidates for BCV therapy over cidofovir to avoid nephrotoxicity. Three out of four patients received cidofovir prior to conversion to BCV. IRB-approved compassionate use of BCV was dosed at 2 mg/kg (max 100 mg) twice weekly PO along with reduced immunosuppression. Resolution of symptoms and HAdV viremia was seen at a mean of 21.5 days (range 15–32) of therapy. All patients had resolution of AKI with a return to baseline creatinine after therapy. Conclusions Though HAdV infection in pediatric SOT patients is uncommon, a subset of patients experience severe disease, morbidity, and graft loss. Currently, HAdV is not routinely monitored in pediatric SOT transplant patients. Although supportive care and decreased immunosuppression remain as the most important component of therapy, BCV was well tolerated and efficacious in our series. Further research is needed to better understand risk factors for HAdV infection and potential antiviral treatment options to improve patient outcomes.

Sign in / Sign up

Export Citation Format

Share Document