Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry

Clinical Proteomics

Vinod Chandran³  Eleftherios P Diamandis¹  Rajiv Gandhi⁴  Ihor Batruch²  Punit Saraon²  Ioannis Prassas²  Daniela Cretu² 

[1] Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada;Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada;Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada;Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Canada

关键词: Mediators;    Proteins;    Selected reaction monitoring assays;    Synovial fluid;    Mass spectrometry;    Proteomics;    Early osteoarthritis;    Psoriatic arthritis;   

Others  :  1026212
DOI  :  10.1186/1559-0275-11-27

 received in 2013-10-23, accepted in 2014-05-01,  发布年份 2014

【 摘 要 】

Background

Synovial fluid (SF) is a dynamic reservoir for proteins originating from the synovial membrane, cartilage, and plasma, and may therefore reflect the pathophysiological conditions that give rise to arthritis. Our goal was to identify and quantify protein mediators of psoriatic arthritis (PsA) in SF.

Methods

Age and gender-matched pooled SF samples from 10 PsA and 10 controls [early osteoarthritis (OA)], were subjected to label-free quantitative proteomics using liquid chromatography coupled to mass spectrometry (LC-MS/MS), to identify differentially expressed proteins based on the ratios of the extracted ion current of each protein between the two groups. Pathway analysis and public database searches were conducted to ensure these proteins held relevance to PsA. Multiplexed selected reaction monitoring (SRM) assays were then utilized to confirm the elevated proteins in the discovery samples and in an independent set of samples from patients with PsA and controls.

Results

We determined that 137 proteins were differentially expressed between PsA and control SF, and 44 were upregulated. The pathways associated with these proteins were acute-phase response signalling, granulocyte adhesion and diapedesis, and production of nitric oxide and reactive oxygen species in macrophages. The expression of 12 proteins was subsequently quantified using SRM assays.

Conclusions

Our in-depth proteomic analysis of the PSA SF proteome identified 12 proteins which were significantly elevated in PsA SF compared to early OA SF. These proteins may be linked to the pathogenesis of PsA, as well serve as putative biomarkers and/or therapeutic targets for this disease.

【 授权许可】

   
2014 Cretu et al.; licensee BioMed Central Ltd.

【 图 表 】

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