title: Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups.
abstract: Current diagnostic tests applied to inflammatory arthritis lack the necessary specificity to appropriately categorise patients. There is a need for novel approaches to classify patients with these conditions. Herein we explored whether urinary proteomic biomarkers specific for different forms of arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA)) or chronic inflammatory conditions (inflammatory bowel disease (IBD)) can be identified. Fifty subjects per group with RA, PsA, OA or IBD and 50 healthy controls were included in the study. Two-thirds of these populations were randomly selected to serve as a training set, while the remaining one-third was reserved for validation. Sequential comparison of one group to the other four enabled identification of multiple urinary peptides significantly associated with discrete pathological conditions. Classifiers for the five groups were developed and subsequently tested blind in the validation test set. Upon unblinding, the classifiers demonstrated excellent performance, with an area under the curve between 0.90 and 0.97 per group. Identification of the peptide markers pointed to dysregulation of collagen synthesis and inflammation, but also novel inflammatory markers. We conclude that urinary peptide signatures can reliably differentiate between chronic arthropathies and inflammatory conditions with discrete pathogenesis.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Siebert
authors.affiliation: Rheumatology Department, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Porter
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Caron
authors.initials: C
authors.lastname: Paterson
authors.affiliation: Rheumatology Department, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors.forename: Rosie
authors.initials: R
authors.lastname: Hampson
authors.affiliation: Gastroenterology Department, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaya
authors.affiliation: Mosaiques Diagnostics, Hannover, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Latosinska
authors.affiliation: Mosaiques Diagnostics, Hannover, Germany.|Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Joost
authors.initials: J
authors.lastname: Schanstra
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Iain
authors.initials: I
authors.lastname: McInnes
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000652:urine*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D010455:Peptides