Pathophysiology of rheumatoid arthritis

To provide a summary of recent advances in the pathophysiology of rheumatoid arthritis.

Highlights include further elucidation of the relationship between the shared epitope, smoking and anticitrullinated protein/peptide antibody generation, including identification of putative citrullinated auto-antigens; and a hypothesis linking citrullinating oral bacteria and anticitrullinated protein/peptide antibody generation. Important work on signalling within regulatory T cells has identified sequestration of protein kinase C theta away from the immune synapse as critical for suppressive activity; TNFα exposure interferes with protein kinase C theta compartmentalisation, explaining its inhibition of regulatory T cell function. Platelet microparticles have emerged as important pro-inflammatory mediators via their stimulatory effects on fibroblast-like synoviocytes. The mechanisms by which fibroblast-like synoviocyte invade are becoming elucidated, and recent work suggests the capacity of these cells to migrate from joint to joint, potentially explaining the evolution of clinical rheumatoid arthritis.

Our knowledge of rheumatoid arthritis pathogenesis continues to expand. The last year has seen some key findings, including the identification of novel, potentially tractable targets for further therapeutic research.