Background/Purpose:

Osteoarthritis (OA) is the most common rheumatic disease. Despite active research in the OA biomarker field, no single protein is sufficiently reliable for its use in diagnosis. This is mainly due to the lack of validation studies in large populations, which makes the findings questionable to be considered as robust biomarkers.

In this work we have undertaken a large-scale study in order to find novel serum proteins that could serve as potential indicators of OA.

Methods:

Antibody suspension bead arrays were applied to profile serum samples from patients with OA (n=288), and compare them to patients with rheumatoid arthritis (RA, n=288), psoriatic arthritis (PSA, n=288) and control (n=96) subjects. The serum protein content was labelled and the protein profiles were obtained using 174 antibodies from the Human Protein Atlas, targeting 78 different proteins. The panel of proteins proposed and analysed for this study was selected on the basis of previous protein profiling studies in the context of rheumatic diseases. A focused bead array was then built to further profile 46 selected protein targets as a replication of the first findings, and also to validate these results in an independent cohort of samples composed by patients with OA (n=196), RA (n=192), PSA (n=192) and control individuals (n=92). For the statistical analysis, a lineal regression analysis adjusting by sex, age and BMI was applied to observe differences in protein profiles between groups. These were denoted statistically significant if they concordantly revealed p.values < 0.05 in the different assays and cohorts.

Results:

Four proteins were found elevated in serum from OA patients compared to controls: S100 calcium binding protein A6 (S100A6), leptin (LEP), Complement 3 (C3) and Inter-Alpha-Trypsin Inhibitor Heavy Chain (ITIH1); and two proteins, Apolipoprotein A-I (APOA1) and Vitamin D-binding protein (GC) were significantly increased in controls compared to OA patients. C3 protein levels also can discriminate among OA, RA and PSA patients being increased in OA patients. ITIH1, a hyaluronic protein carrier, also shows higher protein levels in OA sera compared to RA serum samples. Interestingly, S100A6, a protein involved in chondrocyte differentiation, was also found increased in K&L>2 scores compared to controls (K&L 0 and 1) in both cohorts of samples.

Conclusion:

Broad-scale profiling of protein levels in serum enables the discovery of potential novel biomarkers in osteoarthritis. Using antibody suspension bead arrays we have defined an interesting panel of seven biomarker candidates, which allows distinguishing serum samples from control individuals, OA patients and patients from other rheumatic diseases. The alterations of these proteins provide new potential serum biomarkers of disease, bringing new insights to the OA biomarker field and contributing to a better understanding of OA pathology. Moreover, we have found that S100A6 can be a novel potential early biomarker in OA.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/discovery-of-novel-serum-biomarkers-for-osteoarthritis-using-affinity-proteomics/