Rheumatoid arthritis (RA) is the most common systemic autoimmune condition worldwide. According to a 2005 survey, over one million adults in the United States alone were affected by the disease. RA is characterized by remittent systemic autoimmune inflammation and painful progressive joint deterioration.  It is typically more common in women. 

With the advent of successful biologic disease modifying therapies, the focus of RA therapy has shifted from the induction of immune suppression to the development and maintenance of immune tolerance. However, there are few published data that address the induction and maintenance of immune tolerance based on parallel clinical and mechanistic studies in RA.  Immune tolerance is the notion of retraining the immune system to recognize “self” and not mount a destructive response to “self”, as is the case in autoimmune diseases.  

This approach will lead to the development of novel therapies able to induce disease remission and maintain it with minimal continued therapy.  As with any important field in rapid development, there is a need for a better understanding of how tolerance can be measured and induced in the therapy of human autoimmunity. It is also of critical importance to understand the mechanisms of tolerance induction as the approach may be effective in maintaining disease control. 

Dr. Salvatore Albani, Director and the Charles A.L. and Suzanne M. Stephens Chair in Rheumatology Research at the Arizona Arthritis Center, and Professor of Medicine and Pediatrics at the University of Arizona, and colleagues have been developing a novel approach that directly addresses the need of a tolerogen (a foreign antigen or molecule that induces tolerance) as a complement to currently used biologics. 

The Albani team has recently concluded an National Institutes of Health (NIH) -sponsored, placebo-controlled pilot phase II trial of mucosal tolerization to dnaJP1 in RA. dnaJP1 is a heat shock protein-derived peptide that Albani et al previously identified as a contributor of T cell-mediated inflammation in RA. dnaJP1 treatment led to detectable clinical efficacy, which correlated with a significant reduction in the production of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) by T cells in response to dnaJP1 in vitro.  

The NIH recently reviewed and awarded a research project that will continue the important work started in the Phase II trial.  This will dissect and define the mechanisms (the parts and/or the process) of tolerance from a unique collection of samples obtained from previous trial. 

Using a “bedside back to bench” reverse translational itinerary, this project has the potential to provide valuable information regarding the immunology of human immune tolerance. These studies will also help translate basic immunology concepts into novel tools for designing better trials and predicting treatment efficacy to optimize a patient’s care regimen. 

For more information about the Arizona Arthritis Center and its research, visit its website or call (520)-626-4206.