Abstract
During the development of rheumatoid arthritis (RA) autoantibodies to IgG-Fc, citrullinated proteins, collagen type II (CII), glucose 6 phosphoisomerase (G6PI) and some other self-antigens appear. Of these, a pathogenic effect of the anti-CII and anti-G6PI antibodies is well demonstrated using animal models. These new antibody mediated arthritis models have proven to be very useful for studies involved in understanding the molecular pathways of the induction of arthritis in joints. Both the complement and FcγR systems have been found to play essential roles. Neutrophils and macrophages are important inflammatory cells and the secretion of tumour necrosis factor-α and IL-1β is pathogenic. The identification of the genetic polymorphisms predisposing to arthritis is important for understanding the complexity of arthritis. Disease mechanisms and gene regions studied using the two antibody-induced arthritis mouse models (collagen antibody-induced arthritis and serum transfer-induced arthritis) are compared and discussed for their relevance in RA pathogenesis.
Highlights
Both genetic and environmental factors interact and contribute to the development of autoimmune diseases
The importance of B cells in rheumatoid arthritis (RA) pathogenesis stems from the original finding of high titers of rheumatoid factors (RFs), and from the observation that arthritis is mediated in experimental animals via B cells and anti-collagen type II antibodies [1,2,3,4,5]
In vitro studies with anti-collagen type II (CII) monoclonal antibody (mAb) showed that these antibodies could be pathogenic to chondrocytes even in the absence of inflammatory mediators, being involved in impaired cartilage formation [48], strong inhibition of collagen fibrillogenesis [49] and disorganization of CII fibrils in the extracellular matrix with or without increased matrix synthesis [50]. These mAbs had deleterious effects on the pre-formed cartilage [51]. These findings show that the antibodies initiate the pathogenic events even before the inflammatory phase
Summary
Both genetic and environmental factors interact and contribute to the development of autoimmune diseases. The contributions of antibodies to the disease are initiated by their direct binding to their respective antigens and involve immune complex formation, deposition, and activation of complement and Fc receptors (FcRs).
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