Objective. Induction of immune tolerance to maintain clinical control with a minimal drug regimen is a current research focus in rheumatoid arthritis (RA). Accordingly, we are developing a tolerization approach to dnaJP1, a peptide part of a pathogenic mechanism that contributes to autoimmune inflammation in RA. We undertook this study to test 2 hypotheses: 1) that mucosal induction of immune tolerance to dnaJP1 would lead to a qualitative change from a proinflammatory phenotype to a more tolerogenic functional phenotype, and 2) that immune deviation of responses to an inflammatory epitope might translate into clinical improvement.Methods. One hundred sixty patients with active RA and with immunologic reactivity to dnaJP1 were enrolled in a pilot phase II trial. They received oral doses of 25 mg of dnaJP1 or placebo daily for 6 months.Results. The dnaJP1 peptide was safe and welltolerated. In response to treatment with dnaJP1, there was a significant reduction in the percentage of T cells producing tumor necrosis factor ␣ and a corresponding trend toward an increased percentage of T cells producing interleukin-10. Coexpression of a cluster of molecules (programmed death 1 and its ligands) associated with T cell regulation was also found to be a prerequisite for successful tolerization in clinical responders. AnalyClinicalTrials.gov identifier: NCT00000435.

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Optimizing the management of childhood arthritis requires detailed knowledge of the disease in an individual patient. Advances in 2014 show how in-depth genetic studies and insights into immunopathogenesis could translate into clinical biomarkers and, eventually, individualized therapy.