Immunopathologic aspects of rheumatoid arthritis: who is the conductor and who plays the immunologic instrument?

The inflammatory process of rheumatoid arthritis (RA) resembles a symphony orchestra playing a piece of music--not a song that anyone wants to hear, but a song nevertheless. Each cellular player has a distinct role, and all must coordinate in order to play their discordant "music" successfully. Rheumatoid synovitis consists of resident cells and invading immune cells that together arrange the inflammatory process in RA. There are 3 major types of synovitis that RA can comprise: germinal center synovitis, aggregate synovitis, and diffuse synovitis. Germinal centers are highly organized complex structures that are functionally competent. Aggregates are B cells and T cells arranged in defined follicles, yet they lack germinal center reactions. Diffuse synovitis is the least organized but can still cause significant damage. For each of these types of synovitis, the cellular players and their molecular instruments vary significantly. Differences in lymphoid microorganizations draw attention to the process of lymphoid organogenesis as a fundamental pathway of rheumatoid synovitis, a process that lends stability and sustainability to dysfunctional immune responses. This article will address how tissue-resident and invading cells, in particular T cells, B cells, dendritic cells, and synoviocytes, are brought together in different "symphonic" arrangements and how this process of lymphoid organization affects disease outcome and therapeutic options in RA.