U.S. Department of Energy

Pacific Northwest National Laboratory

Application of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset.

TitleApplication of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset.
Publication TypeJournal Article
Year of Publication2008
AuthorsMetz TO, Qian W-J, Jacobs JM, Gritsenko MA, Moore RJ, Polpitiya AD, Monroe ME, Camp DG, Mueller PW, Smith RD
JournalJ Proteome Res
KeywordsAutoantibodies, Biological Markers, Carrier Proteins, Chondroitin Sulfate Proteoglycans, Chromatography, Liquid, Diabetes Mellitus, Type 1, Follow-Up Studies, Glycoproteins, Humans, Keratan Sulfate, Proteomics, Tandem Mass Spectrometry, Transcortin
Abstract

Novel biomarkers of type 1 diabetes must be identified and validated in initial, exploratory studies before they can be assessed in proficiency evaluations. Currently, untargeted "-omics" approaches are underutilized in profiling studies of clinical samples. This report describes the evaluation of capillary liquid chromatography (LC) coupled with mass spectrometry (MS) in a pilot proteomic analysis of human plasma and serum from a subset of control and type 1 diabetic individuals enrolled in the Diabetes Autoantibody Standardization Program, with the goal of identifying candidate biomarkers of type 1 diabetes. Initial high-resolution capillary LC-MS/MS experiments were performed to augment an existing plasma peptide database, while subsequent LC-FTICR studies identified quantitative differences in the abundance of plasma proteins. Analysis of LC-FTICR proteomic data identified five candidate protein biomarkers of type 1 diabetes. alpha-2-Glycoprotein 1 (zinc), corticosteroid-binding globulin, and lumican were 2-fold up-regulated in type 1 diabetic samples relative to control samples, whereas clusterin and serotransferrin were 2-fold up-regulated in control samples relative to type 1 diabetic samples. Observed perturbations in the levels of all five proteins are consistent with the metabolic aberrations found in type 1 diabetes. While the discovery of these candidate protein biomarkers of type 1 diabetes is encouraging, follow up studies are required for validation in a larger population of individuals and for determination of laboratory-defined sensitivity and specificity values using blinded samples.

DOI10.1021/pr700606w
Alternate JournalJ. Proteome Res.
PubMed ID18092746
PubMed Central IDPMC2672959
Grant List106-310 / / PHS HHS / United States
106-554 / / PHS HHS / United States
107-360 / / PHS HHS / United States
DK070146 / DK / NIDDK NIH HHS / United States
P41 RR018522-05 / RR / NCRR NIH HHS / United States
PL105-33 / / PHS HHS / United States
R33 DK070146-03 / DK / NIDDK NIH HHS / United States
RR18522 / RR / NCRR NIH HHS / United States
| Pacific Northwest National Laboratory