Current serological possibilities for the diagnosis of arthritis with special focus on proteins and proteoglycans from the extracellular matrix

Abstract

This review discusses our current understanding of how the expression and turnover of components of the cartilage extracellular matrix (ECM) have been investigated, both as molecular markers of arthritis and as indicators of disease progression. The cartilage ECM proteome is well studied; it contains proteoglycans (aggrecan, perlecan and inter-α-trypsin inhibitor), collagens and glycoproteins (cartilage oligomeric matrix protein, fibronectin and lubricin) that provide the structural and functional changes in arthritis. However, the changes that occur in the carbohydrate structures, including glycosaminoglycans, with disease are less well studied. Investigations of the cartilage ECM proteome have revealed many potential biomarkers of arthritis. However, a clinical diagnostic or multiplex assay is yet to be realized due to issues with specificity to the pathology of arthritis. The future search for clinical biomarkers of arthritis is likely to involve both protein and carbohydrate markers of the ECM through the application of glycoproteomics.

Keywords:

• arthritis
• collagen
• extracellular matrix
• glycoproteomics
• glycosaminoglycan
• proteoglycan

Financial & competing interests disclosure

MS Lord, BL Farrugia and JM Whitelock have received grant support from the Australian Research Council. MS Lord has also received grant support from the UNSW Gold Star Grant scheme. J Rnjak-Kovacina has received grant support through the UNSW Early Career Researcher Grant Scheme. Finally, JM Whitelock has received support from National Health and Medical Research Council. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Arthritis affects approximately 23% of the adult US population.

• MRI and radiography remain the gold standard to diagnose and monitor arthritis progression. These diagnostic techniques only indicate when arthritis is present. Clinical predictors of arthritis are needed.

• Research devoted to finding molecular markers of arthritis to assist in the diagnosis and analysis of disease progression was started more than 20 years ago, yet no widely adopted biochemical markers of joint changes and disease progression exist.

• The focus of biomarker development has been on the fragmentation of proteins in the cartilage extracellular matrix. This approach has limitations as the proteins present in the cartilage extracellular matrix are not unique to this tissue and the presence of their fragments in the urine, serum and synovial fluid may not be exclusive for the cartilage pathology due to natural turnover processes that occur in tissue maintenance.

• Similarly, changes in the levels of glycosaminoglycans present in urine, serum and synovial fluid as a result of changes in cartilage tissue have also been investigated, but suffer the same lack of specificity as protein fragments.