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

Clinical Proteomics

Ioannis Prassas⁵  Daniela Cretu⁵  Rajiv Gandhi¹  Eleftherios P Diamandis²  Vinod Chandran³  Ihor Batruch⁴  Punit Saraon⁵ 

[1] Arthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaDivision of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, CanadaArthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaArthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaDivision of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, CanadaDivision of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, CanadaArthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaDivision of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, Canada;Arthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaPsoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, CanadaDivision of Rheumatology, Department of Medicine, University of Toronto, Toronto, CanadaArthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaArthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaPsoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, CanadaDivision of Rheumatology, Department of Medicine, University of Toronto, Toronto, CanadaPsoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, CanadaArthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaPsoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, CanadaDivision of Rheumatology, Department of Medicine, University of Toronto, Toronto, CanadaDivision of Rheumatology, Department of Medicine, University of Toronto, Toronto, CanadaArthritis Program, Toronto Western Hospital, University Health Network, Toronto, CanadaPsoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, CanadaDivision of Rheumatology, Department of Medicine, University of Toronto, Toronto, Canada;Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada

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

DOI  :  10.1186/1559-0275-11-27

来源: Humana Press Inc

【 摘 要 】

Abstract

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】

Unknown