Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Barten, Markus J.; Gummert, Jan

doi:10.1159/000101372

Cited by 14 publications

(17 citation statements)

References 60 publications

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“…-Although soluble factors are promising diagnostic markers for the detection of infection, their measurement with enzyme-linked immunosorbent assay (ELISA) is usually performed in batches which may translate to delays in the reporting. As circulating cytokine concentrations may not necessarily reflect biological activities at the cellular level, quantifying cellular response may be a more accurate way of identifying the functional status of responder cells and more closely reflect host inflammatory activity [15,19,20]. With qualified personal available and thorough standardization protocols, the detection of cell surface antigens by flow cytometric technique permits simultaneous quantitative measurement of a receptor panel, identified upon specific cell types or subsets, with a small blood volume (e.g.…”

Section: Role Of Flow Cytometry In the Detection Of Infectionmentioning

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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Section: Role Of Flow Cytometry In the Detection Of Infectionmentioning

confidence: 99%

Flow Cytometric Methods in the Detection of Neonatal Infection

Gille

Orlikowsky²

2007

Transfus Med Hemother

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“…need only minute amounts of biological sample, and are therefore ideal for pediatric patients [60,64]. The concept of predictive medicine by cytomics [65] raises the hope that, by understanding cellular networks, cell systems can be identified that predict individual disease progression, outcome and response to therapy [59,66,67]. Our data suggest that PLE after TCPC type of cardiovascular surgery is possibly associated with immune deficiency as it shows immunological similarities to SLE, celiac disease and ALPS.…”

Section: Discussionmentioning

confidence: 86%

Inflammation and Immune Suppression following Protein Losing Enteropathy after Fontan Surgery Detected by Cytomics

Bocsi

Lenz

Sauer

et al. 2007

Transfus Med Hemother

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Protein losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after total cavopulmonary connection (TCPC - Fontan circulation) surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study aimed to gain insight into immune phenotype alterations following post- TCPC PLE. Patients and Methods: Patients were studied over a period of up to 5 years after surgery. During routine follow-up, blood samples of TCPC patients without (n = 21) and with manifest PLE (n = 12) and of age-matched healthy children (control, n = 22) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Results: Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, C-reactive protein, serum IL-8 and complement activation). In contrast, the lymphocyte count (NK cells, αβ T cell receptor-positive (TCR+) CD4+ cells, αβ TCR+ CD8+ cells) decreased (60-80%, p < 0.001). The residual T cells had elevated CD25 (IL-2R) and CD69 expression. In PLE patients unique cell populations with CD3+ αβ/γδ TCR- and αβ TCR+ CD4- CD8- double negative phenotype were present in increased frequencies. Conclusions: Our studies show for the first time a dramatically altered leukocyte phenotype, the appearance of double negative cells and the alteration of serum compounds after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases such as systemic lupus erythematosus and celiac disease. We conclude that autoimmune processes may play a role in the etiology and pathophysiology of PLE.

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“…Two parametersexpression of CD25 and CD95 on T-cells show impairment of T lymphocyte activation in blood from patients after CPB. Further studies are to show the predictive value of antigen expression on T-cells in respect to clinical outcome (76)(77)(78)(79).…”

Section: Clinical Cytomics In Differentiation Andmentioning

confidence: 99%

Cytomics and nanobioengineering

Pierzchalski¹,

Robitzki²,

Mittag³

et al. 2008

Cytometry Part B Clinical

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The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data.Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery.Focused on small structures, nanobioengineering is the ideal partner of cytomics, the systems biological discipline for cell population analysis. Realizing the idea ''from the molecule to the patient'' develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications.The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine.As the number of scientific data is rising exponentially, new data analysis tools and strategies like cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rationale for cytomics approach. q

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Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Cited by 14 publications

References 60 publications

Flow Cytometric Methods in the Detection of Neonatal Infection

Flow Cytometric Methods in the Detection of Neonatal Infection

Inflammation and Immune Suppression following Protein Losing Enteropathy after Fontan Surgery Detected by Cytomics

Cytomics and nanobioengineering

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