title: Differential gene and protein expression of chemokines and cytokines in synovial fluid of patients with arthritis.
abstract: Psoriatic arthritis (PsA), an inflammatory musculoskeletal disease, develops in approximately 30% of patients with psoriasis. Previously, chemokine (C-X-C motif) ligand 10 (CXCL10) was identified as a predictive biomarker of PsA in patients with psoriasis and was reduced after development of PsA. The purpose of the present study was to explore messenger RNA (mRNA) and protein expression of CXCL10 and its receptor, chemokine (C-X-C motif) receptor 3 (CXCR3), in the joints of patients with PsA to gain insight into their role in the pathogenesis of the disease.
  
  
  
  Sera from 47 patients with PsA and 33 healthy control subjects were compared for expression of CXCL10 by Luminex assay. Synovial fluid (SF) was obtained from patients with PsA (n = 40), osteoarthritis (OA; n = 14), gout (n = 8), and rheumatoid arthritis (RA; n = 11) during clinical care. SF mRNA and protein expression of CXCL10, interleukin-17A (IL-17A), CXCR3, TBX21, RORC and/or interferon γ (IFNγ) were compared among the above-mentioned disease groups, as well as in paired SF and serum samples from patients with PsA using real-time polymerase chain reaction and Luminex assays, respectively.
  
  
  
  Serum CXCL10 was significantly higher in patients with PsA than in control subjects (p = 0.0007). CXCL10, IL-17A, and TBX21 expression were elevated in SF cells of patients with PsA compared with those of patients with OA and gout, but not those of patients with RA. CXCR3 and RORC were elevated in PsA SF cells compared with all other patient groups. Concordant results were obtained for CXCL10 and IL-17A protein expression. IFNγ was elevated in PsA SF compared with OA SF (p = 0.015). CXCL10 protein expression was substantially increased in SF (median 7283.9 pg/ml, interquartile range [IQR] 1330-10,362 pg/ml) compared with paired serum samples (median 282.06, IQR 180.7-395.8 pg/ml; p = 0.001), whereas IFNγ was significantly reduced (SF median 6.03 pg/ml, IQR 4.47-8.94 pg/ml; versus serum median 23.70 pg/ml, IQR 3.2-104.6 pg/ml; p = 0.001).
  
  
  
  CXCL10 may have an important etiological role in PsA that is analogous to that in RA, and it is a candidate biomarker to distinguish PsA from healthy individuals and from patients with OA and gout.
authors.affiliation: Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University of Toronto, University Health Network, 399 Bathurst Street 1E-410B, Toronto, ON, M5T 2S8, Canada.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Muntyanu
authors.affiliation: Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University of Toronto, University Health Network, 399 Bathurst Street 1E-410B, Toronto, ON, M5T 2S8, Canada.
authors.forename: Fatima
authors.initials: F
authors.lastname: Abji
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Kun
authors.initials: K
authors.lastname: Liang
authors.affiliation: Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University of Toronto, University Health Network, 399 Bathurst Street 1E-410B, Toronto, ON, M5T 2S8, Canada.
authors.forename: Remy A
authors.initials: RA
authors.lastname: Pollock
authors.affiliation: Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University of Toronto, University Health Network, 399 Bathurst Street 1E-410B, Toronto, ON, M5T 2S8, Canada.|Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.|Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Vinod
authors.initials: V
authors.lastname: Chandran
authors.affiliation: Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University of Toronto, University Health Network, 399 Bathurst Street 1E-410B, Toronto, ON, M5T 2S8, Canada. dafna.gladman@utoronto.ca.|Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, ON, Canada. dafna.gladman@utoronto.ca.|Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada. dafna.gladman@utoronto.ca.
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
mesh_terms: D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000276:immunology* / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000032:analysis / Q000096:biosynthesis; D016207:Cytokines / Q000032:analysis* / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D054367:Receptors, CXCR3 / Q000032:analysis / Q000096:biosynthesis; D013582:Synovial Fluid / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D054367:Receptors, CXCR3
keywords: Biomarkers; Chemokines; Cytokines; Psoriatic arthritis; Synovial cells; Synovial fluid