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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. IntroductionBoth genetic and environmental factors interact and contribute to the development of autoimmune diseases. One such disease debilitating joint architecture is rheumatoid arthritis (RA). Arthritis in the joint involves a multicellular inflammatory process, including infiltration of lymphocytes and granulocytes into the articular cartilage, proliferation of synovial fibroblasts and macrophages and neovascularization of the synovial lining surrounding the joints. This proliferative process not only induces swelling, erythema, and pain in multiple joints but also progresses to joint destruction and causes loss of bone density and architecture. Many cellular components (macrophages, dendritic cells, fibroblast-like synoviocytes, mast cells, eosinophils, neutrophils, T cells and B cells), cell surface molecules (adhesion molecules, integrins), signaling components (ZAP70, PTPN22, JAK, mitogen activated protein kinase and Stat1) and humoral mediators (antibodies, cytokines, chemokines, metalloproteinases, serine proteases and aggrecanases) interact and aid in the disease progression, leading to digestion of extracelluar matrix and destruction of articular structures.The importance of B cells in RA pathogenesis stems not only from the original finding of high titers of rheumatoid factors (RFs), but also from the observation that arthritis is mediated in experimental animals via B cells and anti-collagen type II (anti-CII) antibodies [1][2][3][4][5]. Interest in studying the role of B cells in arthritis has returned as a result of successful anti-CD20 therapy [6][7][8]. In addition, the two widely used mouse models of antibody-initiated arthritis, collagen antibodyinduced arthritis (CAIA; induced with anti-CII antibodies) and the newly developed serum transfer-induced arthritis (STIA; induced with anti-glucose 6 phosphoisomerase (anti-G6PI) anti-sera) have been better characterized. B cells can contribute to the disease pathogenesis as antigen presenti...

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model

“…The CAIA mice model is induced by injecting an anti-collagen antibody cocktail followed by injections of LPS, it offers several key advantages over the classic collagen-induced arthritis (CIA) model, including a rapid disease onset, synchronicity, high uptake rate, and the capacity to use genetically modified mice, such as transgenics and knockouts [18-20]. This model replicates many aspects of the human effector phase of RA [21]. It occurs independently of any direct activity of B and T cells, allowing effector processes to be studied independently of the events that occur during disease induction [22].…”

“…It occurs independently of any direct activity of B and T cells, allowing effector processes to be studied independently of the events that occur during disease induction [22]. The articular inflammation and cellular infiltration characteristics of the effector stage are attributable to deposited immune complexes and activation of complement and Fc receptors (FcR) [21,23]. Cartilage and bone erosion follows the activation of macrophages, lymphocytes, and synoviocytes and production of MMPs and cytokines [21,22].…”

ASC plays a role in the priming phase of the immune response to type II collagen in collagen-induced arthritis

“…mice in terms of cartilage/bone destruction and expressions of IL-1b and IL-18, indicating that ASC does not noticeably affect the pathogenesis of CAIA. CAIA models are appropriate to study the inflammatory phase of arthritis with regard to neutrophils and macrophages without involving the priming phase of the immune response [35]. Since ASC has been reported to mediate the innate immune response to various pathogen-derived factors [36,37] and environmental insults [38], it accordingly does not appear to be involved in as late a disease phase as that caused by CAIA.…”

Bifunctional Peptide Inhibitors Suppress Interleukin-6 Proliferation and Ameliorates Murine Collagen-Induced Arthritis

“…Although the etiology of RA is not fully understood, it has been suggested that the cause of the disease is the attack on the host joints by immune cells along with the generation of lymphocytes that release inflammatory cytokines such as TNF-α, IFN-γ, and IL-1, IL-6 [2-5]. Th1 cells infiltrate the synovium where they release pro-inflammatory cytokines and chemokines that promote macrophage and neutrophil infiltration and activation [1,4,6]. Th17 cells, a subset of Th cells, have also been implicated in autoimmune diseases, including rheumatoid arthritis [3,7].…”