Autoantibodies as Diagnostic Markers and Mediator of Joint Inflammation in Arthritis

Figure 3

Rheumatoid arthritis pathophysiology. This figure describes different immune cells participating in the initiation, propagation, and tissue damage stages of RA. Environmental factors may trigger generation of posttranslationally modified autoantigens (neo-epitopes) that can be presented by professional antigen-presenting cells to T cells in the context of arthritis-susceptible genetic background. The activation of T cells leads to increased T-B cell cooperation, secretion of cytokines, differentiation of B cells to plasma cells, and production of autoantibodies. These autoantibodies can induce pain as well as inflammation-dependent and inflammation-independent downstream effector mechanisms leading to activation of cells, secretion of proinflammatory cytokines and proteases, which can destroy the cartilage and bone. During this process, neutrophils form NETs, a source for more citrullinated antigens, completing a vicious cycle that can propagate joint inflammation further. CD40: cluster of differentiation 40/co-stimulatory protein present on antigen-presenting cell (APC); CD40L: cluster of differentiation 41-ligand present on Th cell, bind to CD40 to activate APC; TCR: T cell receptor; BCR: B cell receptor; MHC: major histocompatibility complex/surface receptor, with its ligand-activated TCR; FCR: FC receptor/protein receptor present on immune cells; CCR: c-c-motif receptor/beta chemokine receptor; CCL5: chemokine [c-c-motif] ligand-5/RANTES/its chemotactic for neutrophils; CCL2: chemokine [c-c-motif] ligand-2/MCP1; CCL3: chemokine [c-c-motif] ligand-3/MIP-1; CXCL8: IL-8; LTB: TNF-C/induce inflammatory response; VEGF: vascular endothelial growth factor; pannus: abnormal fibrovascular tissue lies over joint surface; MMP: matrix metalloproteinase; PGE: prostaglandin E; IL-1B: interleukin-1-beta; cathepsin k: enzyme controlling bone remodeling; ROS: reactive oxygen species; NO: nitric oxide; IL-4: interleukin-4; IL-10: interleukin-10; IL-13: interleukin-13; T cell: T lymphocyte; B cell: B lymphocyte; TNF: tumor necrosis factor; IL-1: interleukin-1 [192].