Objective: Although oligoarticular juvenile idiopathic arthritis (oJIA) is considered to carry the best prognosis among the JIA subtypes, many children evolve to a chronic course. A few studies have identified clinical risk factors for disease extension, and recent studies have evaluated synovial fluid markers. However, the only biological marker from the serum studied to date is the anti-nuclear antibody (ANA), regarding which there is mixed data regarding prognosis. No studies have evaluated whether additional autoantibodies may affect the articular prognosis of oJIA. Methods: Microarrays containing candidate autoantigens were printed on slides, which were used to profile 36 children with oJIA and 18 controls. Unsupervised cluster analysis was used to identify distinct subgroups of JIA patients. Response to therapy after a mean interval of 4.9 months was evaluated. Results: Cluster analysis revealed two subgroups of oJIA patients, with identical clustering observed when children with onset over age six were excluded. Cluster 1 had higher levels of multiple autoantibodies compared to both cluster 2 as well as controls, including antibodies against several extracellular matrix (ECM) and nuclear antigens. Although the two patient clusters were similar with respect to clinical features and treatment decisions, children in cluster 1 were less likely to have attained remission by the follow-up visit. Conclusion: Antibodies against ECM and possibly other antigens may identify a sub-group of children with oJIA who will require more aggressive therapy to attain control of the arthritis. © Clinical and Experimental Rheumatology 2011.