Application of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset.
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.
Metz
Thomas O
TO
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA. thomas.metz@pnl.gov
Qian
Wei-Jun
WJ
Jacobs
Jon M
JM
Gritsenko
Marina A
MA
Moore
Ronald J
RJ
Polpitiya
Ashoka D
AD
Monroe
Matthew E
ME
Camp
David G
DG
Mueller
Patricia W
PW
Smith
Richard D
RD
D054392:Adipokines; D001323:Autoantibodies; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood / Q000276:immunology; D011508:Chondroitin Sulfate Proteoglycans / Q000097:blood / Q000276:immunology; D002853:Chromatography, Liquid / Q000592:standards; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology*; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood / Q000276:immunology; D006801:Humans; D007632:Keratan Sulfate / Q000097:blood / Q000276:immunology; D000071234:Lumican; D040901:Proteomics; D053719:Tandem Mass Spectrometry / Q000592:standards; D014156:Transcortin / Q000276:immunology / Q000378:metabolism; D000090203:Zn-Alpha-2-Glycoprotein
D054392:Adipokines; D001323:Autoantibodies; D015415:Biomarkers; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D006023:Glycoproteins; D007632:Keratan Sulfate; D000071234:Lumican; D014156:Transcortin; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein; C000604306:LUM protein, human