Skip to main content

An integrated top-down / bottom-up method to identify disease related antibodies


EMSL Project ID
46894

Abstract

We describe the discovery of a new class of biomarkers derived from immunoglobulins using mass spectrometry. We previously investigated this approach in model systems with bottom-up proteomics, and evidence was obtained that it is feasible to identify disease-specific antigen-binding sequences in antibody samples. As a follow-up of this initial work, we propose to develop a method that can be used for a more sensitive, comprehensive and reliable identification of complete disease related antibodies. We will implement new strategies as well as develop novel analytical tools.
While our bottom-up approach is successful in the discovery of biomarkers, it is limited in providing sequence coverage for the immunoglobulins. The main focus of the work that we propose at the PNNL facilities for this project will be the use of advanced techniques (LC and FT-ICR) to study larger fragments of immunoglobulins in a top-down approach. These techniques will result in unraveling the complete primary structures of disease associated immunoglobulins which can potentially be used as therapeutics and to identify autoimmune and tumor associated antigens. Thus, this project aims to produce a new and broadly applicable tool for the identification of disease related antibodies.

Project Details

Project type
Exploratory Research
Start Date
2012-01-10
End Date
2013-02-12
Status
Closed

Team

Principal Investigator

Theo Luider
Institution
Erasmus University Medical Center, Rotterdam

Team Members

Si Wu
Institution
University of Oklahoma

Martijn vanDuijn
Institution
Erasmus University Medical Center, Rotterdam

Leendert Dekker
Institution
Erasmus University Medical Center, Rotterdam

Related Publications

Dekker LJ, S Wu, MM vanDuijn, N Tolic, C Stingl, R Zhao, TN Luider, and L Pasa-Tolic. 2014. "An integrated top-down and bottom-up proteomic approach to characterize the antigen binding fragment of antibodies." Proteomics 14(10):1239-1248. doi:10.1002/pmic.201300366
Liu X, LJ Dekker, S Wu, MM vanDuijn, TN Luider, N Tolic, Q Kou, M Dvorkin, S Alexandrova, K Vyatkina, L Pasa-Tolic, and PA Pevzner. 2014. "De Novo Protein Sequencing by Combining Top-Down and Bottom-Up Tandem Mass Spectra." PNNL-SA-103863, Pacific Northwest National Laboratory, Richland, WA. [Unpublished]