LAUSR

Background Two different phenotypes of hand osteoarthritis (HOA) have been defined: nodal hand osteoarthritis (NHOA) and erosive hand osteoarthritis (EHOA). NHOA involve bone enlargement of the underlying interphalangeal joints, which may typically give rise to Heberden’s nodes, synovitis and swelling. EHOA is a particularly aggressive form characterised by an abrupt onset, as well as signs of inflammation and subchondral erosions. In the absence of efficient diagnostic methods, searching for specific biomarkers for each subtype may help to characterise them. Objectives To define a panel of specific protein markers for the characterisation of EHOA and NHOA and its potential use in clinic. Methods A proteomic approach based on peptide labelling with Isobaric tags for relative and absolute quantitation (iTRAQ) was performed using two different sets of sera (n=55). Samples were classified in 4 groups of study (EHOA, n=10; non-EHOA, n=10; NHOA n=10; non-NHOA, n=5) and 2 control groups (rheumatoid arthritis (RA), n=10 and psoriatic arthritis (PSA), n=10). Serum proteins were digested and peptides from each condition to be compared were differentially labelled with iTRAQ reagents (Sciex). Then, samples were combined and analysed by two-dimensional liquid chromatography coupled to mass spectrometry in a TripleTOF 5600 Mass Spectrometer System (Sciex). Protein identification and quantitation was carried out using ProteinPilot software v.5.0.1. Results A total of 257 different proteins were identify with more than two peptides and a total score ≥2 at 95% confidence. In order to identify specific biomarkers for the characterisation of NHOA and EHOA phenotypes, each group was compared with the non-NHOA or non-EHOA respectively, and also with the control groups. After all the comparisons were made, 26 unique different proteins were found specific of the nodular phenotype. Vasorin (VAS) showed elevated levels in patients diagnosed with NHOA when compared to non-NHOA, RA and PSA groups. On the other hand, 36 unique proteins were identified in those patients with EHOA. Extracellular matrix protein 1 (ECM1) was found with higher concentrations in EHOA than in non-EHOA, RA and PSA patients. In addition, both HOA phenotypes were compared to the control groups and a panel of 30 different proteins were defined. Among these proteins, vascular cell adhesion molecule-1 (VCAM1) was found increased in HOA compared to RA and PSA groups. Conclusions A specific protein profile for the characterisation of EHOA and NHOA disorders has been established. VAS showed elevated levels in patients with NHOA, whereas ECM1 was increased in patients diagnosed with the erosive form of the disease. As none of them were identify in the other phenotype, they might be phenotype-specific biomarkers. In addition, VCAM1 was found with higher levels in both phenotypes of HOA when compared with RA and PSA and might be used to differentiate hand osteoarthritis from other rheumatic diseases. Acknowledgements Financial support (IN606A-2016/012) from the Xunta de Galicia and the European Union (European Social Fund – ESF), is gratefully acknowledged. Disclosure of Interest None declared