Discovery of a new biomarker for the mucopolysaccharidoses (MPS), dipeptidyl peptidase IV (DPP-IV; CD26), by SELDI-TOF mass spectrometry

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• 作者：Clare E. Beesley ; Elisabeth P. Young ; Niamh Finnegan ; Marie Jackson ; Kevin Mills ; Ashok Vellodi ; Maureen Cleary ; Bryan G. Winchester
• 关键词：Mucopolysaccharidoses (MPS) ; Biomarker ; Dipeptidyl peptidase IV (DPP-IV) ; CD26 ; Apolipoprotein-CI and CI′ ; Surface enhanced laser desorption/ionisation time of flight (SELDI-TOF) mass spectrometry
• 刊名：Molecular Genetics and Metabolism
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：96
• 期：4
• 页码：218-224
• 全文大小：383 K

文摘

Surface enhanced laser desorption/ionisation time of flight (SELDI-TOF) mass spectrometry has been used to search for new protein biomarkers in the plasma of patients with mucopolysacharidoses (MPS). Differences in the levels of some plasma proteins, particularly the apolipoprotein ApoCI, were observed between MPS patients and normal controls, using the different chromatographic surfaces (ProteinChips^®). ApoCI was identified by both its mass and by immunological techniques. In plasma, it exists in two forms, ApoCI and a truncated form which lacks two N-terminal amino acids, ApoCI′. In controls, the ratio of ApoCI′:ApoCI observed using the cation-exchange surface (CM10) was approximately 1:2 whereas in most MPS patients it varied from 1:1 to 1:0.8. The ratio of ApoCI′:ApoCI in plasma is determined by the activity of dipeptidyl peptidase IV, DPP-IV (also known as the leucocyte antigen CD26), which was found to be elevated up to 3-fold in MPS patients. The DPP-IV activity decreased in MPS I patients undergoing enzyme replacement therapy, indicating that it could be a useful biomarker for monitoring the efficacy of treatment in MPS disease. As DPP-IV has an important regulatory role in metabolism, it is possible that its elevation could cause some of the secondary pathology in MPS, and inhibition of DPP-IV might have a role in MPS therapy.