Pathogenesis

Rheumatoid arthritis (RA) is an autoimmune disease which is probably initiated by plasma cells in the subsynovial layer of joints which secrete immunoglobulins (mainly IgG and IgM). The latter bind with native IgG and activate complement. Complement activation stimulates leucocyte proliferation and activation.

There may also be a synchronous activation of immune pathways: one of the first histological signs of RA is the infiltration of the synovium with T cells. The T cells may become organised into aggregates. Genetic linkage with HLA-DR genes suggests that the pathogenetic defect may be at the level of antigen presentation, in the context of MHC class II, to T cells.

T cells release cytokines including:

• tumour necrosis factor alpha
• interleukin 1

These cytokines may stimulate:

• synovium to become locally invasive (pannus) with destruction of periarticular soft tissues, articular cartilage and bone
• angiogenesis and the formation of high endothelial venules which accelerate cell infiltration
• secretion of inflammatory mediators and metalloproteinases by synoviocytes