RA is a chronic inflammatory, systemic autoimmune disease of unknown etiology and is characterized by polyarthritis (simultaneous inflammation of several joints) and by extra-articular manifestations as well (see Immunopathology/RA, Joint/RA). Adult RA is commonly associated with a peculiar group of anti-IgG autoantibodies, historically termed rheumatoid factor(s) (RF), which are mainly IgM (but also IgG) immunoglobulins that bind to the Fc component of IgG molecules to form IgG-anti-IgG complexes in the circulation or joint fluid. Although not disease-specific (and detectable in some other connective tissue or infectious diseases or at low titer in some elderly individuals), RF serves as a surrogate marker for adult RA, including examples with extra-articular manifestations. Some other potential surrogate markers apparently showing higher specificity for RA are under study, for example, anti-cyclic citrullinated peptide (anti-CCP) antibodies.

With disease progression of RA, the joint lining (synovial membrane) becomes densely infiltrated by helper and cytolytic T- lymphocytes, by chronic inflammatory cells (macrophages and other cells releasing inflammatory cytokines), and by rheumatoid factor- secreting plasma cells (fully differentiated B-lymphocytes) and germinal centers, all of which extends over the articular cartilage surface as a proliferating and infiltrating inflammatory membrane (rheumatoid pannus) that erodes, destroys, and replaces the underlying cartilage and adjacent bone at areas of contact.

Autoimmune and inflammatory mechanisms of joint injury, including the inflammatory action of cytokines (among them tumor necrosis factor and interleukin-1) released by macrophages and lymphocytes, are major aspects of the pathogenesis of RA and for investigating molecular targets of therapy.

Presented in Table 1 are some of the molecular targets for RA therapy, listed by target, drug/agent and principle mode of action.

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TABLE 1. Introductory Short List of Molecular (and Cellular) Targets of RA Therapy

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