A role for the complement system in rheumatoid arthritis.
The production of autoreactive antibodies from self-reactive B cells results in the formation of immune complexes that deposit in tissue and fix complement, contributing to the pathogenesis of rheumatoid arthritis (RA). Earlier mouse models emphasize the importance of autoreactive antibodies formed against "self" proteins that serve as a source for T cell-mediated immune response, stemming from cross-reactivity and resulting in B cell activity. However, more recent models suggest the need for both autoantibodies and the initiation of the inflammatory cascade via the alternative complement pathway, which is unbridled as the cartilage lacks the usual regulatory proteins of the complement system. Furthermore, deficiencies in specific complement proteins could lead to an escape from negative selection by these self-reactive B cells. Moreover, the classical complement pathway establishes chemotactic gradients by which inflammatory cells follow and accumulate in the synovial fluid where they engulf immune complexes and release proteolytic enzymes. In addition, the processing of circulating immune complexes either via Fc receptor or CR1 and opsonization by complement fragments plays a key role in determining the fate of immune status. In addition, complement proteins are a major determinant in the size and solubility of an immune complex, which also affects clearance. The evidence regarding intra-articular activation of the complement system in RA provides the possibility to pharmacologically manipulate various parts of the complement system for therapeutic purposes and potential therapeutic targets for the control of inflammation and the prevention of joint destruction.
Low
J M
JM
Department of Molecular Microbiology and Immunology, Division of Rheumatology, Saint Louis University School of Medicine, USA. lowjm@slu.edu
Moore
T L
TL
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology*; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans
D003165:Complement System Proteins