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.
Highlights
Osteoarthritis (OA) is the most common rheumatic disease of the developed world and it is increasingly important in current ageing populations, leading to patient chronic disability[1,2,3]
Two proteins identified as distinguishing between OA and controls were quantitatively different between OA patients compared to rheumatoid arthritis (RA) patients (Fig. 1)
We have performed an extensive profiling of serum samples using two different suspension antibody bead arrays with the aim of identifying protein profiles that could be associated with OA
Summary
Osteoarthritis (OA) is the most common rheumatic disease of the developed world and it is increasingly important in current ageing populations, leading to patient chronic disability[1,2,3] This disease manifests by cartilage degradation and as an alteration of the whole joint structure, with progressive synovial inflammation and changes on the subchondral bone and osteophyte formation[4]. Biochemical biomarkers have emerged as promising tools in OA diagnosis, with more sensitivity and reliability than plain radiography to detect joint changes that occur in OA12 Such markers of osteoarthritis could facilitate early diagnosis of joint destruction, disease prognosis and progression monitoring, which could be detectable with an early biochemical test[13]. The specificity of the proteins found was evaluated by screening the protein profiles of RA patients
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