Juvenile Rheumatoid Arthritis (JRA) comprises a heterogeneous group of childhood onset, chronic, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. Little is available by way of laboratory testing to help the pediatric rheumatologist in the initial evaluation of patients although clinical evaluation has been a central and important method of establishing likely diagnoses and outcomes. The sequencing of the human genome and advances in molecular technologies has provided a framework to unravel disease processes. Gene expression analysis is one approach to achieving this end, but it is protein, rather than RNA, that directly mediates disease. Thus, protein expression is likely to provide a better indicator of pathophysiologic pathways than does RNA expression. The field of proteomics, or protein pattern analysis, is the characterization and quantitation of proteins in tissues and body fluids. Disease proteomics has emerged as a rapidly advancing discipline for delineating altered protein expression, identifying novel biomarkers for the diagnosis and early detection of disease, and the identification of new targets for therapeutics. In the first specific aim, we will use a combination of Surface Enhanced Laser Desorption/lonization time of flight mass spectrometry (SELDI-TOF-MS), Cliniprot, and 2-dimensional gel analysis for delineating differential protein expression in peripheral blood and joint fluids to differentiate disease states and between subtypes of JRA. The second specific aim then proposes to identify these differentially expressed proteins and correlate them with the disease state and subtype of JRA. The overall goal of the studies will be to comprehensively identify proteomic profiles and differentially expressed proteins which are likely to be involved in pathogenic pathways in JRA. It will likely lead to greater understanding of the mechanism of disease as well as potentially serve as diagnostic and prognostic indicators of disease. Furthermore, these studies may lead to the identification of novel biomarkers and targets of therapy in JRA.
|Rosenkranz, Margalit E; Wilson, David C; Marinov, Anthony D et al. (2010) Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis. Arthritis Rheum 62:1813-23|