197 research outputs found
Chronic Candida dubliniensis meningitis in a lung transplant recipient
No full textCandida spp. are common colonizers of the oral mucosa and respiratory tract in lung transplant recipients. Although thought to be non-pathogenic in most cases, donor derived infections related to Candida spp. have been described. Among the manifestations of invasive candidiasis, chronic meningitis is one of the rarest and one of the most challenging to diagnose, due to the indolence of the disease and the low yield of the CSF cultures. It is associated with severe morbidity and a high mortality. Fungal PCR and BD glucan assays can be assistance in its diagnosis, although these tests are not widely available. We report a case of a possible donor derived Candida dubliniensis infection in a lung transplant recipient, who initially presented with empyema that was treated successfully, but subsequently developed chronic meningitis. Diagnosis was delayed due to the low yield of CSF cultures, and was confirmed with fungal PCR and BD glucan assay. Keywords: Candida meningitis, Chronic meningitis, Candida dubliniensis, Lung transplant, Immunocompromise
Natural Killer and T-Cell Immunity Pre-transplant as a Predictor for Cytomegalovirus Post-transplant
No full textPre-transplant CMV specific T-cell and NK-cell responses could predict the risk of CMV reactivation following transplantation. We tested this hypothesis in a large cohort of CMV seropositive transplant recipients enrolled in five centers. No patient received antiviral prophylaxis and all had regular viral load monitoring. PBMCs were stimulated with live virus followed by immunophenotyping of T and NK-cell subsets including CD4, CD8, T-reg populations (CD4+CD25+ FOXP3+), CD16, CD56, NKG2C, and IFN-γ. The primary outcome was viremia requiring antiviral therapy within the first 3-months post-transplant. A total of 272 CMV R+ transplant patients were analyzed. Transplant types included kidney (65.4%), liver (23.5%), and other (11.1%). CMV viremia occurred in 83/272(30.7%) and disease in 10/272 (3.7%). This study provides novel insight into pre-transplant evaluation of T and NK cell phenotypes and subsequent risk of CMV reactivation.M.Sc
Natural Killer and T-Cell Immunity Pre-transplant as a Predictor for Cytomegalovirus Post-transplant
No full textPre-transplant CMV specific T-cell and NK-cell responses could predict the risk of CMV reactivation following transplantation. We tested this hypothesis in a large cohort of CMV seropositive transplant recipients enrolled in five centers. No patient received antiviral prophylaxis and all had regular viral load monitoring. PBMCs were stimulated with live virus followed by immunophenotyping of T and NK-cell subsets including CD4, CD8, T-reg populations (CD4+CD25+ FOXP3+), CD16, CD56, NKG2C, and IFN-γ. The primary outcome was viremia requiring antiviral therapy within the first 3-months post-transplant. A total of 272 CMV R+ transplant patients were analyzed. Transplant types included kidney (65.4%), liver (23.5%), and other (11.1%). CMV viremia occurred in 83/272(30.7%) and disease in 10/272 (3.7%). This study provides novel insight into pre-transplant evaluation of T and NK cell phenotypes and subsequent risk of CMV reactivation.M.Sc
Management of Selected Fungal Infections after Transplantation
No full textThis chapter contains sections titled:
Management of selected fungal infections after transplantatio
Comprehensive Immune and Transcriptomic Characterization of Human Cytomegalovirus Infection in Solid Organ Transplant Recipients
No full textHuman cytomegalovirus (HCMV) remains a major cause of morbidity in solid organ transplant (SOT) recipients, especially those with DNAemia. However, its immunologic and transcriptomic features are not well characterized. To explore immune markers linked to relapse, we analyzed exhaustion, activation, and effector markers on global T cells from 33 SOT recipients at DNAemia onset and one month later using flow cytometry. We identified T-cell phenotypes associated with HCMV relapse. Relapsing patients had fewer granzyme B⁺ CD4⁺ T cells at onset and reduced CD154⁺ CD4⁺ T cells after one month. Exhaustion profiling revealed distinct T-cell subsets across groups. In separate cohorts, virus-inclusive single-cell RNA sequencing (scRNA-seq) was performed on SOT recipients with high DNAemia (>10⁵ IU/mL) and lung transplant recipients with chronic lung allograft dysfunction (CLAD). Virus-inclusive sc-RNA-seq showed hematopoietic stem and progenitor cells (HSPCs) and natural killer (NK) cells had broad CMV gene expression and downregulated host pathways. These results define HCMV immunologic and virologic signatures and highlight potential biomarkers or therapeutic targets.M.Sc
Ex-vivo Lung Perfusion Mediated Delivery of Rituximab to Clear Epstein-Barr Virus in Donor Lungs
No full textPosttransplant lymphoproliferative disorder (PTLD) is a serious B-cell malignancy that can arise following solid-organ transplantation. PTLD is especially a risk in transplantations involving an Epstein-Barr virus (EBV)-positive donor and an EBV-negative recipient. In this study we utilize ex-vivo lung perfusion (EVLP), a novel platform for treatment, to administer rituximab to eliminate EBV latently infected B-cells in human donor lungs. We demonstrate that rituximab is effectively delivered using EVLP to B-cells residing in the tissue and lymph nodes of the lungs without inducing adverse effects or acute lung injury. Though the results demonstrate that rituximab does not mediate B-cell or viral depletion during perfusion, we show that the perfused monoclonal antibody can induce B-cell reduction 24 hours post-perfusion in-vitro. Our experiments illustrate the potential of EVLP as a platform to deliver monoclonal antibody therapies to expand the donor pool and make it safer.M.Sc
Ex-vivo Lung Perfusion Mediated Delivery of Rituximab to Clear Epstein-Barr Virus in Donor Lungs
No full textPosttransplant lymphoproliferative disorder (PTLD) is a serious B-cell malignancy that can arise following solid-organ transplantation. PTLD is especially a risk in transplantations involving an Epstein-Barr virus (EBV)-positive donor and an EBV-negative recipient. In this study we utilize ex-vivo lung perfusion (EVLP), a novel platform for treatment, to administer rituximab to eliminate EBV latently infected B-cells in human donor lungs. We demonstrate that rituximab is effectively delivered using EVLP to B-cells residing in the tissue and lymph nodes of the lungs without inducing adverse effects or acute lung injury. Though the results demonstrate that rituximab does not mediate B-cell or viral depletion during perfusion, we show that the perfused monoclonal antibody can induce B-cell reduction 24 hours post-perfusion in-vitro. Our experiments illustrate the potential of EVLP as a platform to deliver monoclonal antibody therapies to expand the donor pool and make it safer.M.Sc
Global and CMV-specific Immune Assays to Predict Clinical Outcomes and Inform Clinical Practice in Solid Organ Transplant Recipients
No full textSolid organ transplantation is an effective procedure for the treatment of end-stage organ failure. However, transplantation can be limited by imprecise immunosuppression and thereby, susceptibility to infections. Assays that measure immune function by quantifying release of cytokines following stimulation of immune cells have shown some predicative value for the development of infections in immunocompromised individuals. This thesis investigates the predictive value, feasibility and clinical benefit of using immune assays in the context of solid organ transplantation. We demonstrated that a newly developed global (innate and adaptive) cell-mediated immune assay called QuantiFERON-Monitor had the ability to quantify the degree of immunosuppression and predict susceptibility of transplant recipients for developing infections. Furthermore, we showed that a cytomegalovirus(CMV)-specific immune assay called QuantiFERON-CMV could predict which patients were susceptible for developing recurrent CMV infections. Finally, we demonstrated that CMV-specific cell-mediated immunity as measured by QuantiFERON-CMV was both feasible and useful in personalizing CMV prophylaxis.M.Sc.2018-05-10 00:00:0
Global and CMV-specific Immune Assays to Predict Clinical Outcomes and Inform Clinical Practice in Solid Organ Transplant Recipients
No full textSolid organ transplantation is an effective procedure for the treatment of end-stage organ failure. However, transplantation can be limited by imprecise immunosuppression and thereby, susceptibility to infections. Assays that measure immune function by quantifying release of cytokines following stimulation of immune cells have shown some predicative value for the development of infections in immunocompromised individuals. This thesis investigates the predictive value, feasibility and clinical benefit of using immune assays in the context of solid organ transplantation. We demonstrated that a newly developed global (innate and adaptive) cell-mediated immune assay called QuantiFERON-Monitor had the ability to quantify the degree of immunosuppression and predict susceptibility of transplant recipients for developing infections. Furthermore, we showed that a cytomegalovirus(CMV)-specific immune assay called QuantiFERON-CMV could predict which patients were susceptible for developing recurrent CMV infections. Finally, we demonstrated that CMV-specific cell-mediated immunity as measured by QuantiFERON-CMV was both feasible and useful in personalizing CMV prophylaxis.M.Sc.2018-05-10 00:00:0
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