Proteomics applied to the clinical follow-up of patients after allogeneic hematopoietic stem cell transplantation

Kaiser, Thorsten; Kamal, Haytham; Rank, Andreas; Kolb, Hans‐Jochem; Holler, Ernst; Ganser, Arnold; Hertenstein, Bernd; Mischak, Harald; Weissinger, Eva M.

doi:10.1182/blood-2004-02-0518

Cited by 156 publications

(126 citation statements)

References 25 publications

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“…Based on CE and MS, urine was analyzed from patients having undergone hematopoietic stem cell transplantation [171]. Sixteen differentially excreted polypeptides formed a pattern of early graft-versus-host disease markers, allowing discrimination of patients with graft-versus-host disease from patients without, with a specificity of 82% and a sensitivity of 100%.…”

Section: Leukemia and Lymphomamentioning

confidence: 99%

Recent advances in blood‐related proteomics

et al. 2005

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Service régional vaudois de transfusion sanguine, Lausanne, SwitzerlandBlood is divided in two compartments, namely, plasma and cells. The latter contain red blood cells, leukocytes, and platelets. From a descriptive medical discipline, hematology has evolved towards a pioneering discipline where molecular biology has permitted the development of prognostic and diagnostic indicators for disease. The recent advance in MS and protein separation now allows similar progress in the analysis of proteins. Proteomics offers great promise for the study of proteins in plasma/serum, indeed a number of proteomics databases for plasma/ serum have been established. This is a very complex body fluid containing lipids, carbohydrates, amino acids, vitamins, nucleic acids, hormones, and proteins. About 1500 different proteins have recently been identified, and a number of potential new markers of diseases have been characterized. Here, examples of the enormous promise of plasma/serum proteomic analysis for diagnostic/prognostic markers and information on disease mechanism are given. Within the blood are also a large number of different blood cell types that potentially hold similar information. Proteomics of red blood cells, until now, has not improved our knowledge of these cells, in contrast to the major progresses achieved while studying platelets and leukocytes. In the future, proteomics will change several aspects of hematology.

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Section: Leukemia and Lymphomamentioning

confidence: 99%

Recent advances in blood‐related proteomics

et al. 2005

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“…The disadvantages include the labor and time necessary and the lack of identification of specific proteins and limited sensitivity for proteins at low levels. 40 Kaiser et al 41 collected urine from transplant recipients and showed that a panel of 16 polypeptides could reliably differentiate patients with GVHD from those without. After refining their sample preparation, the same group analyzed urine samples, using the same methods on a training set of 63 samples, and identified an acute GVHD-specific model of 31 polypetides.…”

Section: Il-2mentioning

confidence: 99%

Biomarkers for acute GVHD: can we predict the unpredictable?

2012

Bone Marrow Transplant

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Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-a, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3a, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized.

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“…[8][9][10][11] The two most important methods that are used to investigate biomarkers, for example, detection of early GVHD, are SELDI-TOF MS and capillary zone electrophoresis mass spectrometry (CE-MS). Although the resolution and sensitivity of SELDI-TOF MS are not as high as those of CE-MS, it has the benefits of relatively low cost and ease of use.…”

Section: Discussionmentioning

confidence: 99%

“…10 The diagnosis of acute GVHD, even before a clinical diagnosis, is possible with the use of a GVHD-specific model consisting of 31 polypeptides. 11 Proteomic analysis has also been applied to the analysis of an allograft response in organ transplantation in animal models.…”

Section: Identification Of Markers For Pirs After Cbt By Seldi-tof Msmentioning

confidence: 99%