title: Identification of urinary peptide biomarkers associated with rheumatoid arthritis.
abstract: Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides. Amongst them, 39 were used to create a classifier model using support vector machine algorithms. Specific peptidic fragments were differentially excreted between groups; fragments of protein S100-A9 and gelsolin were less abundant in rheumatoid arthritis while fragments of uromodulin, complement C3 and fibrinogen were all increasingly excreted. The model generated was subsequently tested in an independent test-set of 31 samples. The classifier demonstrated a sensitivity of 88% and a specificity of 93% in diagnosing the condition, with an area under the receiver operating characteristic curve of 0.93 (p<0.0001). These preliminary results suggest that urinary biomarkers could be useful in the early diagnosis of rheumatoid arthritis. Further studies are currently being undertaken in larger cohorts of patients with rheumatoid arthritis and other athridities to assess the potential of the urinary peptide based classifier in the early detection of rheumatoid arthritis.
authors.affiliation: University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom.
authors.forename: Angelique
authors.initials: A
authors.lastname: Stalmach
authors.affiliation: Western General Infirmary, Edinburgh, United Kingdom.
authors.forename: Hanna
authors.initials: H
authors.lastname: Johnsson
authors.affiliation: University of Glasgow, Institute of Infection, Immunity and Inflammation, Glasgow, United Kingdom.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom.
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.affiliation: Mosaiques-Diagnostics GmbH, Hannover, Germany.
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.affiliation: Mosaiques-Diagnostics GmbH, Hannover, Germany.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dakna
authors.affiliation: University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.affiliation: University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom; Mosaiques-Diagnostics GmbH, Hannover, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: University of Glasgow, Institute of Infection, Immunity and Inflammation, Glasgow, United Kingdom.
authors.forename: Duncan
authors.initials: D
authors.lastname: Porter
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D003176:Complement C3 / Q000652:urine; D005260:Female; D005340:Fibrinogen / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000652:urine*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003176:Complement C3; D010455:Peptides; D005340:Fibrinogen