From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis?

It is believed that therapy for rheumatoid arthritis (RA) is the most effective and beneficial within a short time frame around RA diagnosis. This insight has caused a shift from research in patients with established RA to patients at risk of developing RA and recently diagnosed patients. It is important for improvement of RA therapy to understand when and what changes occur in patients developing RA. This is true for both seropositive and seronegative patients. Activation of the immune system as presented by autoantibodies, increased cytokine and chemokine production, and alterations within several immune cells occur during RA development. In this review we describe RA pathogenesis with a focus on knowledge obtained from patients with arthralgia, pre-RA and recently diagnosed RA. Connections are proposed between altered immune cells, cytokines and chemokines, and events like synovial hyperplasia, pain and bone damage.