title: Quantitative tandem mass-spectrometry of skin tissue reveals putative psoriatic arthritis biomarkers.
abstract: BACKGROUND
  Psoriatic arthritis (PsA) is a distinct inflammatory arthritis occurring in 30% of psoriasis patients. There is a high prevalence of undiagnosed PsA in psoriasis patients; therefore, identifying soluble biomarkers for PsA could help in screening psoriasis patients for appropriate referral to a rheumatologist. Potential PsA biomarkers likely originate in sites of inflammation, such as the skin, and subsequently enter systemic circulation. Our goal was to identify candidate PsA biomarkers by comparing the proteome of skin biopsies obtained from patients with PsA to that from patients with psoriasis without PsA.
  
  
  METHODS
  Skin biopsies were obtained from involved and uninvolved skin of 10 PsA and 10 age/gender-matched psoriasis patients without PsA (PsC). Using strong cation exchange chromatography, followed by label-free quantitative tandem mass spectrometry, we characterized the proteomes of pooled skin samples. Extracted ion current intensities were used to calculate protein abundance ratios, and these were utilized to identify differentially regulated proteins.
  
  
  RESULTS
  Forty-seven proteins were elevated in PsA-derived skin compared to PsC-derived skin. Selected reaction monitoring assays were developed to quantify these potential PsA markers in individual skin samples, and 8 markers were confirmed in an independent sample set. ITGB5 and POSTN were measured in serum samples from 33 PsA and 15 PsC patients, using enzyme-linked immunosorbent assays. ITGB5 was significantly elevated in PsA serum (P < 0.01), and POSTN showed a trend. ITGB5 and POSTN correlated significantly in both patient groups (r = 0.472, P < 0.001).
  
  
  CONCLUSIONS
  Proteomic analysis of PsA and PsC skin identified eight new candidate biomarkers. These markers need to be validated with a larger and independent cohort, in order to delineate their clinical utility in PsA patients. These proteins may also uncover unknown aspects of PsA pathobiology.
authors: 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: Daniela
authors: D
authors: Cretu
authors: Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario Canada.
authors: Kun
authors: K
authors: Liang
authors: 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: Punit
authors: P
authors: Saraon
authors: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario Canada.
authors: Ihor
authors: I
authors: Batruch
authors: 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: Eleftherios P
authors: EP
authors: Diamandis
authors: Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, 399 Bathurst Street, Room 1E 416, Toronto, Ontario M5T 2S8 Canada ; Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario Canada.
authors: Vinod
authors: V
authors: Chandran
keywords: Biomarker; Cutaneous psoriasis; Mass spectrometry; Proteomics; Psoriatic arthritis