Biomarkers for osteoarthritis

Biomarkers are naturally occurring indicators of a biological state. Objectively measured, biomarkers may be used to evaluate normal biological processes, pathogenic (disease) processes or the response to therapeutic and other interventions. For example OA biomarkers might reasonably be expected to include products of OA specific gene expression, antibodies, tissue breakdown products, inflammatory cytokines etc. Dr Sharif and collaborators have used the SELDI-TOF-MS proteomic technique to analyse protein expression changes in 284 serum samples from patients with knee OA of varying severity. This is classified according to the establish Kellgren & Lawrence (K&L) scoring system which gives a score in the range of 0 to 4 (low to high severity). OA serum samples were also compared to suitable control groups. These comprised serum samples provided by healthy individuals (n=36) and patients with rheumatoid arthritis (n=25). Proteins that gave similar signal in all K&L groups of OA patients were ignored, while proteins that were up or down regulated were selected for further study. Three of the biomarkers were found to be up-regulated in OA patients and increased with increasing K&L scores. Two of these markers have been identified as the proteins V65 vitronectin fragment and complement C3f peptide. The third biomarker could not be identified due to technical difficulties and may be included in any patent filing within the priority year. This initial study suggests that V65 and Cf3 can discriminate OA from controls with specificity of 97% and 92% respectively. A fourth biomarker was found to be down regulated in samples from patients with K&L scores >2 and has been identified as CTAPIII protein. All 4 novel serum biomarkers have significant correlations with clusters of parameters reflecting the decline in cartilage metabolism, in local inflammation and the continuous bone remodelling as OA progresses. These correlations suggest that these new serum biomarkers might also have pathophysiological relevance and could represent interesting new starting points to better understand OA.