Systemic immune markers characterizing early stages of rheumatoid arthritis

Abstract

Rheumatoid arthritis is a chronic autoimmune disease occurring in ~1% of the world population. The main feature of the disease is ongoing joint inflammation, caused by immune cells and their soluble factors, leading to irreversible bone erosions and cartilage damage. Early treatment can halt progression of the disease and development of irreversible damage. Early recognition is therefore very important. Present research is geared at recognizing development of RA as early as possible by identifying high risk individuals before definite clinical symptoms of RA develop. Interestingly, although the joints are the target of the immune system in RA, it is a systemic disease which may start elsewhere in the body. This notion is supported by the emergence of antibodies against self antigens (autoantibodies directed at citrullinated proteins (ACPA) and rheumatoid factor (RF)) and an increase of inflammatory markers in the blood, which may occur years before RA diagnosis. Several studies have shown that seropositive (ACPA and/or RF positive) arthralgia patients are at risk to develop RA. Thus, in order to prevent RA progression, it is important to identify specific alterations within the immune system that are involved in the switch from the high-risk state to full-blown disease. Our general aim was to define peripheral immune alterations in seropositive arthralgia patients and in newly diagnosed RA patients. This approach allowed the identification of systemic immune markers that may be involved in disease development. In addition, we identified immune alterations which may contribute to the worsening of joint inflammation in long-standing RA patients