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

J Proteome Res. 2008 Feb;7(2):698-707. doi: 10.1021/pr700606w. Epub 2007 Dec 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipokines
  • Autoantibodies*
  • Biomarkers / blood
  • Carrier Proteins / blood
  • Carrier Proteins / immunology
  • Chondroitin Sulfate Proteoglycans / blood
  • Chondroitin Sulfate Proteoglycans / immunology
  • Chromatography, Liquid / standards
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / immunology*
  • Follow-Up Studies
  • Glycoproteins / blood
  • Glycoproteins / immunology
  • Humans
  • Keratan Sulfate / blood
  • Keratan Sulfate / immunology
  • Lumican
  • Proteomics*
  • Tandem Mass Spectrometry / standards
  • Transcortin / immunology
  • Transcortin / metabolism

Substances

  • AZGP1 protein, human
  • Adipokines
  • Autoantibodies
  • Biomarkers
  • Carrier Proteins
  • Chondroitin Sulfate Proteoglycans
  • Glycoproteins
  • LUM protein, human
  • Lumican
  • Transcortin
  • Keratan Sulfate