Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory disease resulting from an autoimmune response to self-antigens, leading to inflammation of synovial tissue of joints and subsequent cartilage and bone erosion. Current disease-modifying anti-rheumatic drugs and biologic inhibitors of TNF, IL-6, T cells and B cells block inflammation nonspecifically, which may lead to adverse effects, including infection. They do not generally induce long-term drug-free remission or restoration of immune tolerance to self-antigens, and lifelong treatment is usual. The development of antigen-specific strategies in RA has so far been limited by insufficient knowledge of autoantigens, of the autoimmune pathogenesis of RA and of the mechanisms of immune tolerance in man. Effective tolerance-inducing antigen-specific immunotherapeutic strategies hold promise of greater specificity, of lower toxicity and of a longer-term solution for controlling or even preventing RA. This paper reviews current understanding of autoantigens and their relationship to immunopathogenesis of RA, and emerging therapeutics that aim to leverage normal tolerance mechanisms for implementation of antigen-specific therapy in RA.

Piperlongumine Suppresses Dendritic Cell Maturation by Reducing Production of Reactive Oxygen Species and Has Therapeutic Potential for Rheumatoid Arthritis

“…Increasing evidence has shown that DCs may be attractive targets for the treatment of autoimmune diseases, such as RA (36,37). For instance, injection of immature DCs attenuates CIA by inducing in vivo expansion of CD49b + regulatory T cells (38).…”

Regulatory dendritic cell therapy: From rodents to clinical application

“…This combination of DCreg with citrullinated peptides was given the name Rheumavax, and patients received a single dose intradermally. Citrullinated self-Ags have emerged as a major group of post-translationally modified auto-Ags in RA and are found in inflamed RA joints [56]. As in the autoimmune diabetes trial at the University of Pittsburgh, the vaccine was well-tolerated and no adverse effects were observed.…”

Dendritic Cell Immune Therapy to Break or Induce Tolerance

“…This phase I study assessed the safety of repetitive intradermal administration of tolerogenic DCs in adult type 1 diabetes (T1D) patients. A second phase I study has been conducted in rheumatoid arthritis (RA) patients treated with a single intradermal injection of autologous DCs cultured with an inhibitor of (NF-κB) signaling (BAY 11-7082) and pulsed with citrullinated peptides [87]. Both treatments were safe and well tolerated and paved the way to developing clinical studies to test the efficacy of tolerogenic DC immunotherapy in T1D and RA and after kidney transplantation.…”