Stratification and Monitoring of Juvenile Idiopathic Arthritis Patients by Synovial Proteome Analysis

Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset,autoimmune diseases with variable clinical outcomes. We investigated whether profiling of the synovialfluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguishpatients in whom inflammation extends to affect a large number of joints, early in the disease process.SF samples from 22 JIA patients were analyzed: 10 with oligoarticular arthritis, 5 extended oligoarticularand 7 polyarticular disease. SF samples were labeled with Cy dyes and separated by two-dimensionalelectrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patientsubgroups. Proteins were identified using MALDI-TOF mass spectrometry with expression furtherverified by Western immunoblotting and immunohistochemistry. Hierarchical clustering based on theexpression levels of a set of 40 proteins segregated the extended oligoarticular from the oligoarticularpatients (p < 0.05). Expression patterns of the isolated protein panel have also been observed overtime, as disease spreads to multiple joints. The data indicates that synovial fluid proteome profilescould be used to stratify patients based on risk of disease extension. These protein profiles may alsoassist in monitoring therapeutic responses over time and help predict joint damage.