Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays

A pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs.Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis.The NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.Juvenile idiopathic arthritis (JIA) is an autoimmune disease and the second most common disease of childhood after diabetes, affecting approximately one in every 1,000 children [1]. JIA consists of a clinically heterogeneous group of arthritic disorders that begin before age 16 years and persist for more than 6 weeks. The cause and pathogenesis of JIA are still poorly understood. Chronic inflammation of joints is the only common denominator for all JIA patients. Of the seven subsets of JIA iden