Novel apoptosis assay to analyze immunosuppression

Boldt, Andreas; Barten, Markus J.; Weiß, Claudia; Sagner, Anja; Mohr, Friedrich W.; Gummert, Jan

doi:10.1002/cyto.a.20218

Cited by 9 publications

(6 citation statements)

References 10 publications

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“…Nevertheless, our apoptosis assay provided insights into mechanisms of drug monotherapy. Thus, we detected a stronger effect on apoptosis in T cells for MPA compared to SRL or TRL, whereas CsA has no effect [21], confirming a previous study [25]. Evaluating the effects of different drug combinations we showed that overall MPA plus TRL had a greater impact on inhibition of T cell proliferation, and to a lesser extent on T cell surface antigens, than all other drug combinations [13].…”

Section: In Vitro Studiessupporting

confidence: 77%

“…Additionally, T helper 1 (TH1) and TH2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α und INF-γ) were detected in the serum using multiplex bead array analysis [20]. Apoptotic T cells were quantified using the fluorescent annexin V, and the TUNEL assay was used to detect DNA breaks [21]. The myeloid and plasmocytoid dendritic cell subsets in whole blood were determined without stimulation by specific gating strategies to distinguish these two lineages from leukocytes [22].…”

Section: Flow Cytometrymentioning

confidence: 99%

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Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Barten¹,

Gummert²

2007

Transfus Med Hemother

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Conventional therapeutic drug monitoring based on measuring of blood concentrations (pharmacokinetic) 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 (pharmacodynamic) because, due to the genetic heterogeneity, the immune systems of the 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 drugs effects on immune cell functions. Against this background we developed assays which are based on whole blood, flow cytometry and biomarkers of diverse functions of T cells and of dendritic cell subsets. These biomarker assays allow us to differentiate between synergistic and antagonistic pharmacodynamic effects of an immunosuppressive drug combination therapy in vitro and to predict the pharmacodynamic drug effects in heart-transplanted recipients. Such a pharmacodynamic drug monitoring based on biomarkers may offer the opportunity to complete conventional therapeutic drug monitoring and, therefore, to tailor immunosuppressive therapy more individually.

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Section: In Vitro Studiessupporting

confidence: 77%

Section: Flow Cytometrymentioning

confidence: 99%

Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Barten¹,

Gummert²

2007

Transfus Med Hemother

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“…Recent studies have reported that rapamycin impairs viability in several cell types (22,38,39). In this study, it was clearly demonstrated that rapamycin not only affects the differentiation of the porcine NPCCs after transplantation but also suppresses cell expansion.…”

Section: Discussionmentioning

confidence: 73%

Rapamycin Suppresses the Expansion and Differentiation of Porcine Neonatal Pancreas Cell Clusters

et al. 2010

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“…These instruments have features that can even surpass flow cytometry by minimizing required sample volume by one order of magnitude [50] and increasing the number of simultaneously analyzable parameters per cell [51,52]. Based on increased multiplexing, high-content analysis of cell populations becomes available [53] that would increase our understanding of infection development and may lead to predictive medicine [54][55][56] for preventive therapy [57][58][59]. To date, no flow cytometric marker or set of markers is sensitive and specific enough to allow neonatologists to withhold antibiotic treatment of a sick infant who is suspected to be seriously infected.…”

Section: Discussionmentioning

confidence: 99%

Flow Cytometric Methods in the Detection of Neonatal Infection

Gille

Orlikowsky²

2007

Transfus Med Hemother

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Bacterial infection remains the main cause of neonatal morbidity and mortality. With clinical signs unspecific and little, its course is fulminant, and only early antibiotic therapy protects from death or major adverse sequelae. Methods: Conventional diagnostic tests have shortcomings and are only partly suitable to identify infected vs. non-infected newborns. There is a fast increasing demand for standardized flow cytometric techniques in the detection of neonatal infection which require minimal amounts of blood. Target cells are monocytes/ macrophages, granulocytes and NK cells. Results: The choice of receptors and interpretation of results need to be done carefully: A variety of receptors are expressed differently, basally or upon cytokine-mediated regulation, in full- or preterm neonates than in adults, and their expression is influenced by perinatal confounders. Examples are HLA-DR, CD80, CD86, CD16, CD32 receptors on monocytes/macrophages. Flow cytometric measurement of CD11b and CD64 expression on phagocytes combined with cytokine (IL-6 or IL-8) or C-reactive protein measurement in plasma or whole blood have turned out to be most sensitive and specific markers for detecting early- and late-onset bacterial infection. Conclusion: To date, no flow cytometric marker or set of markers is sensitive and specific enough to allow neonatologists to withhold antibiotic treatment of a sick neonate who is suspected to be infected.

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Novel apoptosis assay to analyze immunosuppression

Cited by 9 publications

References 10 publications

Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Rapamycin Suppresses the Expansion and Differentiation of Porcine Neonatal Pancreas Cell Clusters

Flow Cytometric Methods in the Detection of Neonatal Infection

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