Treatment of inflammatory disease.

Using proteomics, in a search for the initiating autoantigen in RA, we discovered, isolated and identified a powerful immunomodulatory protein, BiP. Human in vitro studies have investigated the effect of BiP on the activation of human peripheral blood monocytes and differentiation of dendritic cells (DC) and regulatory T cells (CD4+/CD8+). In parallel, BiP has been shown to have prophylactic and therapeutic action in the murine collagen–induced arthritis (CIA) disease model. The therapeutic effect of BiP in CIA appears to be long-lived suggesting a re-education of the immune system to produce regulatory cells which have been used to resolve CIA in adoptive transfer experiments. Thus BiP is the first human protein to be described that will induce functional regulatory cells by intravenous administration and in vitro in human mononuclear cell cultures.