title: Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry.
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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cretu
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Prassas
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Punit
authors.initials: P
authors.lastname: Saraon
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ihor
authors.initials: I
authors.lastname: Batruch
authors.affiliation: Arthritis Program, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Room 1E 416, Toronto, ON M5T 2S8, Canada ; Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Canada.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gandhi
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada ; Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.affiliation: Arthritis Program, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Room 1E 416, Toronto, ON M5T 2S8, Canada ; Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada ; Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Vinod
authors.initials: V
authors.lastname: Chandran
keywords: Early osteoarthritis; Mass spectrometry; Mediators; Proteins; Proteomics; Psoriatic arthritis; Selected reaction monitoring assays; Synovial fluid
references.citation: N Engl J Med. 2009 Jul 30;361(5):496-509
references.pmid: 19641206
references.citation: J Proteomics. 2012 Jun 6;75(10):2869-78
references.pmid: 22245418
references.citation: Proteomics. 2005 May;5(8):2247-57
references.pmid: 15846842
references.citation: Genome Biol. 2009;10(11):R130
references.pmid: 19919682
references.citation: Curr Rheumatol Rep. 2012 Aug;14(4):349-57
references.pmid: 22592745
references.citation: Arthritis Rheum. 2006 Aug;54(8):2665-73
references.pmid: 16871531
references.citation: Proteome Sci. 2011 Oct 11;9:65
references.pmid: 21988904
references.citation: Annu Rev Biomed Eng. 2009;11:49-79
references.pmid: 19400705
references.citation: J Am Acad Dermatol. 2011 May;64(5):879-87
references.pmid: 21315480
references.citation: J Pediatr (Rio J). 2000 Mar-Apr;76(2):125-32
references.pmid: 14647685
references.citation: Hum Immunol. 2013 Oct;74(10):1333-8
references.pmid: 23916976
references.citation: Clin Rev Allergy Immunol. 2013 Apr;44(2):149-56
references.pmid: 22274791
references.citation: Biochem J. 1988 Feb 15;250(1):81-5
references.pmid: 2833238
references.citation: Am J Sports Med. 2003 Jan-Feb;31(1):83-6
references.pmid: 12531763
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2012 Jan-Feb;4(1):15-37
references.pmid: 21826801
references.citation: J Rheumatol. 1990 May;17(5):695-7
references.pmid: 2359083
references.citation: J Rheumatol. 2003 Aug;30(8):1719-24
references.pmid: 12913926
references.citation: Biochim Biophys Acta. 2013 Aug;1834(8):1581-90
references.pmid: 23567906
references.citation: Mol Cell Proteomics. 2008 Oct;7(10):2019-27
references.pmid: 18669619
references.citation: J Invest Dermatol. 2008 May;128(5):1207-11
references.pmid: 18200064
references.citation: J Rheumatol. 1982 Sep-Oct;9(5):719-22
references.pmid: 6757423
references.citation: J Leukoc Biol. 2005 Apr;77(4):476-86
references.pmid: 15629886
references.citation: Nat Biotechnol. 2008 Dec;26(12):1367-72
references.pmid: 19029910
references.citation: Eur J Immunol. 1999 Jul;29(7):2119-29
references.pmid: 10427974
references.citation: Curr Opin Rheumatol. 2013 May;25(3):287-96
references.pmid: 23492739
references.citation: Hum Hered. 1994 Mar-Apr;44(2):72-6
references.pmid: 8188313
references.citation: Clin Chem Lab Med. 2013 Feb;51(2):317-25
references.pmid: 23096109
references.citation: J Proteome Res. 2011 Apr 1;10(4):1794-805
references.pmid: 21254760
references.citation: Proteomics. 2011 Dec;11(23):4551-8
references.pmid: 21932441
references.citation: Proteomics. 2011 Mar;11(6):1148-52
references.pmid: 21365756
references.citation: Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii14-7
references.pmid: 15708927
references.citation: Arthritis Rheum. 1999 Jul;42(7):1481-4
references.pmid: 10403277
references.citation: ISRN Dermatol. 2013 May 30;2013:630620
references.pmid: 23819059
references.citation: Trends Genet. 2010 Sep;26(9):415-23
references.pmid: 20692714
references.citation: J Pathol. 2002 Nov;198(3):369-77
references.pmid: 12375270
references.citation: Proteomics. 2005 Aug;5(13):3531-6
references.pmid: 16041672
references.citation: Rheumatology (Oxford). 1999 May;38(5):431-40
references.pmid: 10371281
references.citation: Blood. 2011 Dec 1;118(23):6107-14
references.pmid: 21926348
references.citation: Anal Chem. 2002 Sep 15;74(18):4741-9
references.pmid: 12349978
references.citation: J Proteome Res. 2012 Mar 2;11(3):1503-11
references.pmid: 22188163
references.citation: Am J Clin Dermatol. 2003;4(7):441-7
references.pmid: 12814334
references.citation: Mol Cancer Ther. 2011 Nov;10(11):2083-93
references.pmid: 21859838
references.citation: J Rheumatol. 2008 Jul;35(7):1434-7
references.pmid: 18609740
references.citation: BMC Med. 2012 Apr 19;10:39
references.pmid: 22515324
references.citation: Nat Chem Biol. 2005 Oct;1(5):252-62
references.pmid: 16408053
references.citation: Crit Rev Clin Lab Sci. 2013 Feb-Apr;50(2):51-63
references.pmid: 23758541
references.citation: Br J Dermatol. 1989 Feb;120(2):239-44
references.pmid: 2538138
references.citation: Immunology. 2014 Feb;141(2):133-42
references.pmid: 23819583
references.citation: J Proteome Res. 2012 Jul 6;11(7):3880-7
references.pmid: 22681384
references.citation: Int Immunol. 1998 Aug;10(8):1185-96
references.pmid: 9723705
references.citation: Mol Cell Proteomics. 2009 Oct;8(10):2339-49
references.pmid: 19596694