Project description:The COVID-19 pandemic has significantly changed organ donation and transplantation worldwide. Since the beginning of the pandemic, the uncertainty regarding the potential route of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created tremendous pressures on transplantation communities, and international organisations have advised against using organs from deceased donors who have tested positive for SARS-CoV-2. The possibility of SARS-CoV-2 transmission through organ donation has only been reported for lung transplantation; hence, based on current experience, transplantation of non-lung organs from donors with active SARS-CoV-2 infection has been considered possible and safe, at least over short-term follow-up. As the evolving outbreak of SARS-CoV-2 continues, alongside the presence of vaccines and new treatment options, clinicians should consider transplanting organs from deceased donors with active SARS-CoV-2 infection to recipients with limited opportunities for transplantation and those with specific natural or vaccine-induced immunity. This article proffers an expert opinion on the use of organs from deceased donors with resolved or active SARS-CoV-2 infection in the absence of more definitive data and standardised acceptance patterns.
Project description:We report the transmission of acute myeloid leukemia (AML) undetected at donation from a deceased organ donor to two kidneys and one liver recipients. We reviewed the medical records, and performed molecular analyses and whole exome sequencing (WES) to ascertain AML donor origin and its molecular evolution. The liver recipient was diagnosed 11 months after transplantation and died from complications 2 months later. The two kidney recipients (R1 and R2) were diagnosed 19 and 20 months after transplantation and both received treatment for leukemia. R1 died of complications 11 months after diagnosis, while R2 went into complete remission for 44 months, before relapsing. R2 died 10 months later of complications from allogenic bone marrow transplantation. Microsatellite analysis demonstrated donor chimerism in circulating cells from both kidney recipients. Targeted molecular analyses and medical records revealed NPM1 mutation present in the donor and recipients, while FLT3 was mutated only in R1. These findings were confirmed by WES, which revealed additional founder and clonal mutations, and HLA genomic loss in R2. In conclusion, we report the first in-depth genomic analysis of AML transmission following solid organ transplantation, revealing distinct clonal evolution, and providing a potential molecular explanation for tumor escape.
Project description:We recovered Bartonella quintana DNA from dental pulp of a domestic cat. This study, the first to detect B. quintana in a nonhuman mammal, changes our understanding of the epidemiology of this infection and proposes that cats may be an emerging source of human infection.
Project description:We provide the first evidence that Bartonella quintana can infect dogs and cause typical signs of endocarditis. Using PCR and sequencing, we identified B. quintana in the blood of a dog from the United States with aortic valve endocarditis and probably also in the mitral valve of a dog from New Zealand with endocarditis.
Project description:Following solid organ transplantation, a substantial proportion of chronic allograft loss is attributed to the formation of donor-specific antibodies (DSAs) and antibody-mediated rejection (AbMR). The frequency and phenotype of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells is altered in the setting of kidney transplantation, particularly in patients who develop AbMR. However, the roles of Tfh and Tfr cells in AbMR after solid organ transplantation is unclear. We developed mouse models to inducibly and potently perturb Tfh and Tfr cells to assess the roles of these cells in the development of DSA and AbMR. We found that Tfh cells are required for both de novo DSA responses as well as augmentation of DSA following presensitization. Using orthotopic allogeneic kidney transplantation models, we found that deletion of Tfh cells at the time of transplantation resulted in less severe transplant rejection. Furthermore, using inducible Tfr cell deletion strategies we found that Tfr cells inhibit de novo DSA formation but only have a minor role in controlling kidney transplant rejection. These studies demonstrate that Tfh cells promote, whereas Tfr cells inhibit, DSA to control rejection after kidney transplantation. Therefore, targeting these cells represent a new therapeutic strategy to prevent and treat AbMR.
Project description:During the two World Wars, Bartonella quintana was responsible for trench fever and is now recognised as an agent of re-emerging infection. Many reports have indicated widespread B. quintana exposure since the 1990s. In order to evaluate its prevalence in ancient populations, we used real-time PCR to detect B. quintana DNA in 400 teeth collected from 145 individuals dating from the 1st to 19th centuries in nine archaeological sites, with the presence of negative controls. Fisher's exact test was used to compare the prevalence of B. quintana in civil and military populations. B. quintana DNA was confirmed in a total of 28/145 (19.3%) individuals, comprising 78 citizens and 67 soldiers, 20.1% and 17.9% of which were positive for B. quintana bacteraemia, respectively. This study analysed previous studies on these ancient samples and showed that the presence of B. quintana infection followed the course of time in human history; a total of 14/15 sites from five European countries had a positive prevalence. The positive rate in soldiers was higher than those of civilians, with 20% and 18.8%, respectively, in the 18th and 19th centuries, but the difference in frequency was not significant. These results confirmed the role of dental pulp in diagnosing B. quintana bacteraemia in ancient populations and showed the incidence of B. quintana in both civilians and soldiers.
Project description:Although major advances have been made in solid organ and hematopoietic stem cell transplantation in the last 50 years, big challenges remain. This review outlines the current immunological limitations for hematopoietic stem cell and solid organ transplantation and discusses new immune-modulating therapies in preclinical development and in clinical trials that may allow these obstacles to be overcome.