Quantitative measurement of a candidate serum biomarker peptide derived from α2-HS-glycoprotein, and a preliminary trial of multidimensional peptide analysis in females with pregnancy-induced hypertension
| Autor: | Hiroshi Fujiwara, Daisuke Nonaka, Hitoshi Ishikawa, Yoshihiko Araki, Kenji Takamori, Yasuka Miyakuni, Michio Banzai, Koyo Yoshida, Michio Nojima, Satoru Takeda, Tanaka Kenji, Hiroshi Yoshitake, Mitsuaki Yanagida, Kensuke Hamamura, Mayumi Sakuraba |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Peptide analysis 030213 general clinical medicine alpha-2-HS-Glycoprotein Clinical Biochemistry Peptide Mass Spectrometry Matrix (chemical analysis) 03 medical and health sciences 0302 clinical medicine Serum biomarkers Pregnancy Disease biomarker Humans chemistry.chemical_classification Chromatography dBm General Medicine Hypertension Pregnancy-Induced 030104 developmental biology chemistry Immunology Pregnancy induced Female Glycoprotein Peptides Biomarkers Chromatography Liquid |
| Zdroj: | Annals of clinical biochemistry. 55(2) |
| ISSN: | 1758-1001 |
| Popis: | PurposeWe previously attempted to develop quantitative enzyme-linked immunosorbent assay (ELISA) systems for the PDA039/044/071 peptides, potential serum disease biomarkers (DBMs) of pregnancy-induced hypertension (PIH), primarily identified by a peptidomic approach (BLOTCHIP®-mass spectrometry (MS)). However, our methodology did not extend to PDA071 (cysteinyl α2-HS-glycoprotein341–367), due to difficulty to produce a specific antibody against the peptide. The aim of the present study was to establish an alternative PDA071 quantitation system using liquid chromatography-multiple reaction monitoring (LC-MRM)/MS, to explore the potential utility of PDA071 as a DBM for PIH.MethodsWe tested heat/acid denaturation methods in efforts to purify serum PDA071 and developed an LC-MRM/MS method allowing for specific quantitation thereof. We measured serum PDA071 concentrations, and these results were validated including by three-dimensional (3D) plotting against PDA039 (kininogen-1439–456)/044 (kininogen-1438–456) concentrations, followed by discriminant analysis.ResultsPDA071 was successfully extracted from serum using a heat denaturation method. Optimum conditions for quantitation via LC-MRM/MS were developed; the assayed serum PDA071 correlated well with the BLOTCHIP® assay values. Although the PDA071 alone did not significantly differ between patients and controls, 3D plotting of PDA039/044/071 peptide concentrations and construction of a Jackknife classification matrix were satisfactory in terms of PIH diagnostic precision.ConclusionsCombination analysis using both PDA071 and PDA039/044 concentrations allowed PIH diagnostic accuracy to be attained, and our method will be valuable in future pathophysiological studies of hypertensive disorders of pregnancy. |
| Databáze: | OpenAIRE |
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