Epitope-specific immunotherapy of rheumatoid arthritis: Clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial†

摘要: Objective Induction of immune tolerance to maintain clinical control with a minimal drug regimen is current research focus in rheumatoid arthritis (RA). Accordingly, we are developing tolerization approach dnaJP1, peptide part pathogenic mechanism that contributes autoimmune inflammation RA. We undertook this study test 2 hypotheses: 1) mucosal induction dnaJP1 would lead qualitative change from proinflammatory phenotype more tolerogenic functional phenotype, and 2) deviation responses an inflammatory epitope might translate into improvement. Methods One hundred sixty patients active RA immunologic reactivity were enrolled pilot phase II trial. They received oral doses 25 mg or placebo daily for 6 months. Results The was safe well-tolerated. In response treatment there significant reduction the percentage T cells producing tumor necrosis factor α corresponding trend toward increased interleukin-10. Coexpression cluster molecules (programmed death 1 its ligands) associated cell regulation also found be prerequisite successful responders. Analysis primary efficacy end point (meeting American College Rheumatology 20% improvement criteria at least once on day 112, 140, 168) showed difference between groups became post hoc analysis using generalized estimating equations. Differences 140 followup. Post combination hydroxychloroquine (HCQ) superior HCQ placebo. Conclusion Tolerization leads efficacy. Susceptibility relies coexpression can down-regulate adaptive immunity.