Analysis of Autoantibody Profiles
in Osteoarthritis
Using Comprehensive Protein Array Concepts
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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