Background
Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints leading to irreversible joint destruction. To prevent and/or slow down progressive joint destruction, the diagnosis of RA at early stage in the disease is important. The autoantibodies against citrullinated proteins (aCCP) provide such ability, representing a marker for early RA. However, a remarkable variety in the reactivity against different citrulline-containing peptides has been described, which indicates that not only citrulline but also its flanking amino acid sequences play a role in the antigenicity and that autoantibodies recognizing such targets are poly-clonal. Furthermore, B cells isolated from synovial fluid of aCCP-positive RA patients were shown to produce aCCP antibodies spontaneously, whereas peripheral blood B cells require a stimulation to produce these antibodies. The predominance of IgG production in synovial fluid and synovial tissue was observed in comparison with serum. These findings altogether provide the evidence for the local antigen-driven maturation of B cells into aCCP-producing plasma cells within inflamed RA synovium due to the presence of citrullinated synovial proteins.