Rheumatoid arthritis: an editorial perspective based on cytokine imbalance

Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are distinct systemic rheumatic and autoimmune diseases with overlapping clinical features and laboratory findings. Although the majority of patients fit the textbook descriptions of these disorders, there are occasional patients whose illness defies precise diagnostic classification. Examples are mixed connective tissue disease, rheumatoid arthritis and systemic vasculitis, and the overlap SS/SLE syndrome with anti-Ro autoantibodies [1]. Cytokine abnormalities are prominent in all rheumatic diseases. This editorial focuses on cytokine abnormalities in RA and particularly in the rheumatoid synovium, but because of these disease interrelationships has implications for SS and SLE as well. The pathology in RA can be dominated by the systemic features, particularly when rheumatoid lung, severe vasculitis or Felty's syndrome are present. Rheumatoid factor was the first autoantibody to be extensively studied from functional, pathological and immunogenetic aspects. For most patients, however, joint inflammation with its predilection to progress to joint destruction comes to dominate the clinical picture. For the clinical immunologist, the ability to study synovial fluid and cells offers an investigative opportunity not generally found in other rheumatic diseases, i.e. to take measurements where the action is, directly at the site of autoimmune attack. Careful histopathologic studies performed decades ago are the basis for our understanding of immunopathogenic events in the rheumatoid synovium. These studies highlight the intense chronic inflammatory activity with activated macrophages, lymphocytic and plasma cell infiltration, germinal center formation, and tissue destruction. Local production of rheumatoid factor and immune complexes, as well as complement consumption, were demonstrated 20 years ago in an investigative era dominated by humoral immunity.(ABSTRACT TRUNCATED AT 250 WORDS)