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

Abstract

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 synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish patients 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 oligoarticular and 7 polyarticular disease. SF samples were labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with expression further verified by Western immunoblotting and immunohistochemistry. Hierarchical clustering based on the expression levels of a set of 40 proteins segregated the extended oligoarticular from the oligoarticular patients (p < 0.05). Expression patterns of the isolated protein panel have also been observed over time, as disease spreads to multiple joints. The data indicates that synovial fluid proteome profiles could be used to stratify patients based on risk of disease extension. These protein profiles may also assist in monitoring therapeutic responses over time and help predict joint damage.

Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

“…[24][25][26] Unlike synovial fluid, AH protein expression profiles did not seem to correlate with JIA subtype, however, the number of patients is too low for a reliable analysis. TTR was not identified in synovial fluid by other studies or in our SELDI-ToF MS experiments employing synovial fluids from patients with JIA (data not shown).…”

Psoriatic Arthritis Under a Proteomic Spotlight: Application of Novel Technologies to Advance Diagnosis and Management

“…As a targeted peptide-centric approach, MRM has been used for multiple biomarker studies in the past few years to detect and quantify biomarkers in a range of diseases (Table 1) [112][113][114][115][116][117][118][119][120][121][122][123]. MRM assays can be multiplexed to support the measurement and quantification of 100 s of important candidate biomarker proteins simultaneously in several hundreds of patient tissue or serum samples.…”

Secretion of pro‐inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast‐like synoviocytes in juvenile idiopathic arthritis

“…Work has been done on the proteomic profile of synovial fluid from JIA 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, yet we do not have an understanding of the contribution attributable to the FLS in the disease. JIA FLS proved to be active, aggressive cells in the disease process, with profuse release of inflammatory cytokines, chemokines and loss of control over destructive mediators.…”