title: Analysis of autoantibody profiles in osteoarthritis using comprehensive protein array concepts.
abstract: Osteoarthritis (OA) is the most common rheumatic disease and one of the most disabling pathologies worldwide. To date, the diagnostic methods of OA are very limited, and there are no available medications capable of halting its characteristic cartilage degeneration. Therefore, there is a significant interest in new biomarkers useful for the early diagnosis, prognosis, and therapeutic monitoring. In the recent years, protein microarrays have emerged as a powerful proteomic tool to search for new biomarkers. In this study, we have used two concepts for generating protein arrays, antigen microarrays, and NAPPA (nucleic acid programmable protein arrays), to characterize differential autoantibody profiles in a set of 62 samples from OA, rheumatoid arthritis (RA), and healthy controls. An untargeted screen was performed on 3840 protein fragments spotted on planar antigen arrays, and 373 antigens were selected for validation on bead-based arrays. In the NAPPA approach, a targeted screening was performed on 80 preselected proteins. The autoantibody targeting CHST14 was validated by ELISA in the same set of patients. Altogether, nine and seven disease related autoantibody target candidates were identified, and this work demonstrates a combination of these two array concepts for biomarker discovery and their usefulness for characterizing disease-specific autoantibody profiles.
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , Stockholm SE 171- 21, Sweden.
authors.forename: Frauke
authors.initials: F
authors.lastname: Henjes
authors.forename: Lucía
authors.initials: L
authors.lastname: Lourido
authors.forename: Cristina
authors.initials: C
authors.lastname: Ruiz-Romero
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Tajes
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
authors.forename: María
authors.initials: M
authors.lastname: Gonzalez-Gonzalez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Manuel
authors.initials: M
authors.lastname: Fuentes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000276:immunology*; D040081:Protein Array Analysis / Q000379:methods; D015203:Reproducibility of Results; D015238:Sulfotransferases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D015238:Sulfotransferases; C438013:dermatan-4-sulfotransferase-1
keywords: NAPPA; Protein microarrays; autoantibody profiles; osteoarthritis