title: Discovery of circulating proteins associated to knee radiographic osteoarthritis.
abstract: Currently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.
authors.affiliation: Rheumatology Division, ProteoRed/ISCIII Proteomics Group, INIBIC - Hospital Universitario de A Coruña, A Coruña, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Lourido
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Burcu
authors.initials: B
authors.lastname: Ayoglu
authors.affiliation: Wellcome Trust Centre For Human Genetics, McCarthy's Group, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Tajes
authors.affiliation: Rheumatology Division, ProteoRed/ISCIII Proteomics Group, INIBIC - Hospital Universitario de A Coruña, A Coruña, Spain.
authors.forename: Natividad
authors.initials: N
authors.lastname: Oreiro
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Frauke
authors.initials: F
authors.lastname: Henjes
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hellström
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Jochen M
authors.identifier: 0000-0001-8141-8449
authors.initials: JM
authors.lastname: Schwenk
authors.affiliation: Rheumatology Division, ProteoRed/ISCIII Proteomics Group, INIBIC - Hospital Universitario de A Coruña, A Coruña, Spain.|CIBER-BBN Instituto de Salud Carlos III, INIBIC-CHUAC, A Coruña, Spain.
authors.forename: Cristina
authors.identifier: 0000-0001-7649-9803
authors.initials: C
authors.lastname: Ruiz-Romero
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Rheumatology Division, ProteoRed/ISCIII Proteomics Group, INIBIC - Hospital Universitario de A Coruña, A Coruña, Spain. fblagar@sergas.es.|RIER-RED de Inflamación y Enfermedades Reumáticas, INIBIC-CHUAC, A Coruña, Spain. fblagar@sergas.es.
authors.forename: Francisco J
authors.identifier: 0000-0001-9821-7635
authors.initials: FJ
authors.lastname: Blanco
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000175:diagnosis*; D040901:Proteomics / Q000379:methods; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers