1.
Use of (1→3)-β-d-glucan for diagnosis and management of invasive mycoses in HIV-infected patients.
Farhour, Z, Mehraj, V, Chen, J, Ramendra, R, Lu, H, Routy, JP
Mycoses. 2018;(10):718-722
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Abstract
People living with HIV (PLHIV) are highly vulnerable to invasive fungal infections (IFIs) due to their immune dysfunction. Diagnosis and treatment of IFIs remain challenging due to the requirement of deep tissue sampling to visualise and culture fungi before initiating treatment. Such techniques are less practical in resource-limited settings due to their cost and requirement of relatively invasive procedures. Hence, identification of surrogate markers for the early diagnosis and therapeutic monitoring of IFIs is required. Recent studies have shown that (1→3)-β-d-glucan (BDG), a major fungal cell wall antigen, represents a promising soluble marker for the presumptive diagnosis and therapeutic monitoring of IFIs in HIV-infected patients. Herein, we review findings on the merits of BDG assays in the diagnosis of IFIs and monitoring of antifungal therapies for PLHIV. Conversely to other types of immunocompromised patients, HIV infection is associated with gut damage and subsequent bacterial and fungal translocation leading to elevated BDG plasma levels.
2.
Flow cytometry-based pharmacodynamic monitoring after organ transplantation.
Dieterlen, MT, Eberhardt, K, Tarnok, A, Bittner, HB, Barten, MJ
Methods in cell biology. 2011;:267-84
Abstract
Conventional therapeutic drug monitoring based on measuring immunosupressive drug concentrations in blood is important in the clinical management of immunosuppressive therapy in transplantation medicine. Since rejection or infection occurs at irregular drug concentrations immunosuppressive drug therapy is often empiric and prophylactic in nature. In addition, blood immunosuppressant levels are only indirect predictors of the pharmacologic effects on immune cells, because the genetic heterogeneity the immune systems of transplant recipients are not equally sensitive to drug effects. Therefore, therapeutic drug monitoring requires the application of reliable and effective methods to study the pharmacodynamic variability by direct measurements of drug effects on immune cell functions. Flow cytometry offers a multiplicity of quantitative analysis possibilities, from detection of phosphorylated molecules up to complex multicolor analysis of whole blood samples. A large spectrum of flow cytometry-based applications for pharmacodynamic monitoring is available and allows detection and analysis of diverse function of T cells and dendritic cell subsets. By combining several assays, it is possible to generate a broad picture of the immune status of every single transplanted recipient. Furthermore, it is even possible to differentiate between synergistic and antagonistic pharmacodynamic effects of immunosuppressive drug combination therapy in vitro and to predict the pharmacodynamic drug effects in transplanted recipients. Such a pharmacodynamic drug monitoring may offer the opportunity to complete conventional therapeutic drug monitoring and, therefore, to tailor immunosuppressive therapy more individually.