Following a proposal made by the French and German Ministers for Foreign Affairs at the November 2020 Paris Peace Forum, 4 global partners, the Food and Agriculture Organization (FAO), the World ...Organization for Animal Health (OIE), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO), in May 2021 established the interdisciplinary One Health High-Level Expert Panel (OHHLEP) (https://www.who.int/groups/one-health-high-level-expert-panel) to enhance their cross-sectoral collaboration. There is no shortage of “One Health” definitions in the published literature and among institutions and organizations. ...an immediate priority for OHHLEP was to develop consensus around a working definition as a solid basis to support a common understanding among the panel members and the partner organizations. Key underlying principles including 1. equity between sectors and disciplines; 2. sociopolitical and multicultural parity (the doctrine that all people are equal and deserve equal rights and opportunities) and inclusion and engagement of communities and marginalized voices; 3. socioecological equilibrium that seeks a harmonious balance between human–animal–environment interaction and acknowledging the importance of biodiversity, access to sufficient natural space and resources, and the intrinsic value of all living things within the ecosystem; 4. stewardship and the responsibility of humans to change behavior and adopt sustainable solutions that recognize the importance of animal welfare and the integrity of the whole ecosystem, thus securing the well-being of current and future generations; and 5. transdisciplinarity and multisectoral collaboration, which includes all relevant disciplines, both modern and traditional forms of knowledge and a broad representative array of perspectives. PLoS Pathog 18(6): e1010537. https://doi.org/10.1371/journal.ppat.1010537 About the Authors: One Health High-Level Expert Panel (OHHLEP) Wiku B. Adisasmito Affiliation: Universitas Indonesia, Depok, West Java, Indonesia Salama Almuhairi Affiliation: National Emergency Crisis and Disasters Management Authority, Abu Dhabi, United Arab Emirates Casey Barton Behravesh Affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America Pépé Bilivogui Affiliation: World Health Organization, Guinea Country Office, Conakry, Guinea Salome A. Bukachi Affiliation: Institute of Anthropology, Gender and African Studies, University of Nairobi, Nairobi, Kenya Natalia Casas Affiliation: National Ministry of Health, Autonomous City of Buenos Aires, Argentina Natalia Cediel Becerra Affiliation: School of Agricultural Sciences, Universidad de La Salle, Bogotá, Colombia Dominique F. Charron Affiliation: International Development Research Centre, Ottawa, Canada Abhishek Chaudhary Affiliation: Indian Institute of Technology (IIT), Kanpur, India Janice R. Ciacci Zanella Affiliation: Brazilian Agricultural Research Corporation (Embrapa), Embrapa Swine and Poultry, Concórdia, Santa Catarina, Brazil Andrew A. Cunningham Affiliation: Institute of Zoology, Zoological Society of London, London, United Kingdom Osman Dar Affiliations Global Operations Division, United Kingdom Health Security Agency, London, United Kingdom, Global Health Programme, Chatham House, Royal Institute of International Affairs, London, United Kingdom Nitish Debnath Affiliation: Fleming Fund Country Grant to Bangladesh, DAI Global, Dhaka, Bangladesh Baptiste Dungu Affiliations Afrivet B M, Pretoria, South Africa, Faculty of Veterinary Science, University of Kinshasa, Kinshasa, Democratic Republic Congo Elmoubasher Farag Affiliation: Ministry of Public Health, Health Protection & Communicable Diseases Division, Doha, Qatar George F. Gao Affiliation: Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China David T. S. Hayman Affiliation: Molecular Epidemiology and Public Health Laboratory, Massey University, Palmerston North, New Zealand Margaret Khaitsa Affiliation: Mississippi State University, Starkville, Mississippi,
Summary Background Rejection of allografts has always been the major obstacle to transplantation success. We aimed to improve characterisation of different kidney-allograft rejection phenotypes, ...identify how each one is associated with anti-HLA antibodies, and investigate their distinct prognoses. Methods Patients who underwent ABO-compatible kidney transplantations in Necker Hospital and Saint-Louis Hospital (Paris, France) between Jan 1, 1998, and Dec 31, 2008, were included in our population-based study. We assessed patients who provided biopsy samples for acute allograft rejection, which was defined as the association of deterioration in function and histopathological lesions. The main outcome was kidney allograft loss—ie, return to dialysis. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology, C4d in allograft biopsies, and donor-specific anti-HLA antibodies. Findings 2079 patients were included in the main analyses, of whom 302 (15%) had acute biopsy-proven rejection. We identified four distinct patterns of kidney allograft rejection: T cell-mediated vascular rejection (26 patients 9%), antibody-mediated vascular rejection (64 21%), T cell-mediated rejection without vasculitis (139 46%), and antibody-mediated rejection without vasculitis (73 24%). Risk of graft loss was 9·07 times (95 CI 3·62–19·7) higher in antibody-mediated vascular rejection than in T cell-mediated rejection without vasculitis (p<0·0001), compared with an increase of 2·93 times (1·1–7·9; P=0·0237) in antibody-mediated rejection without vasculitis and no significant rise in T cell-mediated vascular rejection (hazard ratio HR 1·5, 95% CI 0·33–7·6; p=0·60). Interpretation We have identified a type of kidney rejection not presently included in classifications: antibody-mediated vascular rejection. Recognition of this distinct phenotype could lead to the development of new treatment strategies that could salvage many kidney allografts. Funding None.
In addition to scalability, human embryonic stem cells (hESCs) have the unique advantage of allowing their directed differentiation toward lineage-specific cells.
This study tested the feasibility of ...leveraging the properties of hESCs to generate clinical-grade cardiovascular progenitor cells and assessed their safety in patients with severe ischemic left ventricular dysfunction.
Six patients (median age 66.5 years interquartile range (IQR): 60.5 to 74.7 years; median left ventricular ejection fraction 26% IQR: 22% to 32%) received a median dose of 8.2 million (IQR: 5 to 10 million) hESC-derived cardiovascular progenitors embedded in a fibrin patch that was epicardially delivered during a coronary artery bypass procedure. The primary endpoint was safety at 1 year and focused on: 1) cardiac or off-target tumor, assessed by imaging (computed tomography and fluorine-18 fluorodeoxyglucose positron emission tomography scans); 2) arrhythmias, detected by serial interrogations of the cardioverter-defibrillators implanted in all patients; and 3) alloimmunization, assessed by the presence of donor-specific antibodies. Patients were followed up for a median of 18 months.
The protocol generated a highly purified (median 97.5% IQR: 95.5% to 98.7%) population of cardiovascular progenitors. One patient died early post-operatively from treatment-unrelated comorbidities. All others had uneventful recoveries. No tumor was detected during follow-up, and none of the patients presented with arrhythmias. Three patients developed clinically silent alloimmunization. All patients were symptomatically improved with an increased systolic motion of the cell-treated segments. One patient died of heart failure after 22 months.
This trial demonstrates the technical feasibility of producing clinical-grade hESC-derived cardiovascular progenitors and supports their short- and medium-term safety, thereby setting the grounds for adequately powered efficacy studies. (Transplantation of Human Embryonic Stem Cell-derived Progenitors in Severe Heart Failure ESCORT; NCT02057900)
Display omitted
The clinical importance of preexisting HLA antibodies at the time of transplantation, identified by contemporary techniques, is not well understood. We conducted an observational study analyzing the ...association between preexisting donor-specific HLA antibodies (HLA-DSA) and incidence of acute antibody-mediated rejection (AMR) and survival of patients and grafts among 402 consecutive deceased-donor kidney transplant recipients. We detected HLA-DSA using Luminex single-antigen assays on the peak reactive and current sera. All patients had a negative lymphocytotoxic cross-match test on the day of transplantation. We found that 8-year graft survival was significantly worse (61%) among patients with preexisting HLA-DSA compared with both sensitized patients without HLA-DSA (93%) and nonsensitized patients (84%). Peak HLA-DSA Luminex mean fluorescence intensity (MFI) predicted AMR better than current HLA-DSA MFI (P = 0.028). As MFI of the highest ranked HLA-DSA detected on peak serum increased, graft survival decreased and the relative risk for AMR increased: Patients with MFI >6000 had >100-fold higher risk for AMR than patients with MFI <465 (relative risk 113; 95% confidence interval 31 to 414). The presence of HLA-DSA did not associate with patient survival. In conclusion, the risk for both AMR and graft loss directly correlates with peak HLA-DSA strength. Quantification of HLA antibodies allows stratification of immunologic risk, which should help guide selection of acceptable grafts for sensitized patients.
Abstract
Aims
The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles ...(EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation.
Methods and results
Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages.
Conclusions
EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.
Graphical Abstract
Melanoma is the most aggressive skin cancer in humans that often expresses MHC class II (MHC II) molecules, which could make these tumors eliminable by the immune system. However, this MHC II ...expression has been associated with poor prognosis, and there is a lack of immune-mediated eradication. The lymphocyte activation gene-3 (LAG-3) is a natural ligand for MHC II that is substantially expressed on melanoma-infiltrating T cells including those endowed with potent immune-suppressive activity. Based on our previous data showing the signaling capacity of MHC II in melanoma cells, we hypothesized that LAG-3 could contribute to melanoma survival through its MHC II signaling capacity in melanoma cells. In this study, we demonstrate that both soluble LAG-3 and LAG-3-transfected cells can protect MHC II-positive melanoma cells, but not MHC II-negative cells, from FAS-mediated and drug-induced apoptosis. Interaction of LAG-3 with MHC II expressed on melanoma cells upregulates both MAPK/Erk and PI3K/Akt pathways, albeit with different kinetics. Inhibition studies using specific inhibitors of both pathways provided evidence of their involvement in the LAG-3-induced protection from apoptosis. Altogether, our data suggest that the LAG-3-MHC II interaction could be viewed as a bidirectional immune escape pathway in melanoma, with direct consequences shared by both melanoma and immune cells. In the future, compounds that efficiently hinder LAG-3-MHC II interaction might be used as an adjuvant to current therapy for MHC II-positive melanoma.
Lyme disease is the commonest vector-borne zoonosis in the temperate world, and an emerging infectious disease in Canada due to expansion of the geographic range of the tick vector Ixodes scapularis. ...Studies suggest that climate change will accelerate Lyme disease emergence by enhancing climatic suitability for I. scapularis. Risk maps will help to meet the public health challenge of Lyme disease by allowing targeting of surveillance and intervention activities.
A risk map for possible Lyme endemicity was created using a simple risk algorithm for occurrence of I. scapularis populations. The algorithm was calculated for each census sub-division in central and eastern Canada from interpolated output of a temperature-driven simulation model of I. scapularis populations and an index of tick immigration. The latter was calculated from estimates of tick dispersion distances by migratory birds and recent knowledge of the current geographic range of endemic I. scapularis populations. The index of tick immigration closely predicted passive surveillance data on I. scapularis occurrence, and the risk algorithm was a significant predictor of the occurrence of I. scapularis populations in a prospective field study. Risk maps for I. scapularis occurrence in Canada under future projected climate (in the 2020s, 2050s and 2080s) were produced using temperature output from the Canadian Coupled Global Climate Model 2 with greenhouse gas emission scenario enforcing 'A2' of the Intergovernmental Panel on Climate Change.
We have prepared risk maps for the occurrence of I. scapularis in eastern and central Canada under current and future projected climate. Validation of the risk maps provides some confidence that they provide a useful first step in predicting the occurrence of I. scapularis populations, and directing public health objectives in minimizing risk from Lyme disease. Further field studies are needed, however, to continue validation and refinement of the risk maps.
One Health action for health security and equity Adisasmito, Wiku B; Almuhairi, Salama; Barton Behravesh, Casey ...
The Lancet (British edition),
02/2023, Letnik:
401, Številka:
10376
Journal Article
Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. To analyze the effect of ...anti-HLA antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using Luminex™ platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Among 62 recipients (23%) who had anti-HLA antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA antibodies (DSA) (7 were donor-specific anti-HLA antibodies for single unrelated cord blood transplant and 7 for double unrelated cord blood transplant). Donor specific anti-HLA antibodies threshold ranged from 1620-17629 of mean fluorescence intensity (MFI). Cumulative incidence of Day-60 neutrophil engraftment was 76%: 44% for recipients with donor specific anti-HLA antibodies and 81% in those without donor specific anti-HLA antibodies (P=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor specific anti-HLA antibodies and 32% in those without antibodies (P=0.06). The presence of donor specific anti-HLA antibodies was associated with a trend for decreased survival rate (42% vs. 29%; P=0.07). Donor specific anti-HLA antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient's screening for donor specific anti-HLA antibodies before unrelated cord blood transplantation is recommended before choosing an HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit for which the patient has donor specific anti-HLA antibodies.
PDF
