NDLI: Human biomarker discovery and predictive models for disease progression for idiopathic pneumonia syndrome following allogeneic stem cell transplantation.

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Human biomarker discovery and predictive models for disease progression for idiopathic pneumonia syndrome following allogeneic stem cell transplantation.

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Human biomarker discovery and predictive models for disease progression for idiopathic pneumonia syndrome following allogeneic stem cell transplantation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Schlatzer, Daniela M. Dazard, Jean-Eudes Ewing, Rob M. Ilchenko, Serguei Tomcheko, Sara E. Eid, Saada Ho, Vincent Yanik, Greg Chance, Mark R. Cooke, Kenneth R.
Description	Country affiliation: United States Author Affiliation: Schlatzer DM ( Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.)
Abstract	Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative therapy for many malignant and nonmalignant conditions. Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication that limits successful outcomes. Preclinical models suggest that IPS represents an immune mediated attack on the lung involving elements of both the adaptive and the innate immune system. However, the etiology of IPS in humans is less well understood. To explore the disease pathway and uncover potential biomarkers of disease, we performed two separate label-free, proteomics experiments defining the plasma protein profiles of allogeneic SCT patients with IPS. Samples obtained from SCT recipients without complications served as controls. The initial discovery study, intended to explore the disease pathway in humans, identified a set of 81 IPS-associated proteins. These data revealed similarities between the known IPS pathways in mice and the condition in humans, in particular in the acute phase response. In addition, pattern recognition pathways were judged to be significant as a function of development of IPS, and from this pathway we chose the lipopolysaccaharide-binding protein (LBP) protein as a candidate molecular diagnostic for IPS, and verified its increase as a function of disease using an ELISA assay. In a separately designed study, we identified protein-based classifiers that could predict, at day 0 of SCT, patients who: 1) progress to IPS and 2) respond to cytokine neutralization therapy. Using cross-validation strategies, we built highly predictive classifier models of both disease progression and therapeutic response. In sum, data generated in this report confirm previous clinical and experimental findings, provide new insights into the pathophysiology of IPS, identify potential molecular classifiers of the condition, and uncover a set of markers potentially of interest for patient stratification as a basis for individualized therapy.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
DOI	10.1074/mcp.M111.015479
Journal	Molecular & Cellular Proteomics
Issue Number	6
Volume Number	11
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2012-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics Blood Proteins Metabolism Hematopoietic Stem Cell Transplantation Adverse Effects Models, Biological Pneumonia Blood Acute-phase Proteins Isolation & Purification Anti-inflammatory Agents, Non-steroidal Therapeutic Use Biological Markers Capillary Electrochromatography Case-control Studies Disease Progression Etanercept Immunoglobulin G Drug Therapy Etiology Pathology Principal Component Analysis Proteomics Receptors, Tumor Necrosis Factor Reproducibility Of Results Transplantation, Homologous Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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