J Korean Med Assoc.  2010 Oct;53(10):853-861. 10.5124/jkma.2010.53.10.853.

Pathogenesis of rheumatoid arthritis

• Kim JM
• Kim HY

• KMID: 2188410
• DOI: http://doi.org/10.5124/jkma.2010.53.10.853

Abstract

Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder, characterized by synovitis and severe joint destruction. Many mechanisms are considered to be implicated in the development and progression of the disease. It may be important to understand differences in the pathogenesis of RA at various stages of its process. Early autoimmune changes begin before the onset of clinical arthritis. During this period, various autoantibodies such as rheumatoid factor and anticyclic citrullinated peptide antibody can be produced by the interaction between B and T cell activated by aberrant immune responses, triggered by external or self antigens. This is followed by a local inflammatory transitional phase, in which complex biochemical processes are involved in molecular and structural changes of the joint. The primary inflammatory site is the synovium. Synovial infiltration with mononuclear cells, especially CD4+ T cells, macrophages, and B cells leads to an articular, pathologic phase. In this phase, proinflammatory cytokines including tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 as well as inflammatory mediators such as prostaglandin E2 and proteases can be produced by various cell to cell interaction occuring in the synovium, which may finally result in the destruction of synovium, cartilage and bone. Although the pathogenesis of RA is intricate and remains unclear, understanding and identifying its pathogenesis is important in revealing the appropriate therapeutic target that may lead to significant clinical benefits.

Keyword

Rheumatoid arthritis; Pathogenesis; Therapeutic target

MeSH Terms

Arthritis
Arthritis, Rheumatoid
Autoantibodies
Autoantigens
B-Lymphocytes
Biochemical Processes
Cartilage
Cell Communication
Cytokines
Dinoprostone
Interleukin-1beta
Interleukin-6
Joints
Macrophages
Peptide Hydrolases
Rheumatoid Factor
Synovial Membrane
Synovitis
T-Lymphocytes
Tumor Necrosis Factor-alpha
Autoantibodies
Autoantigens
Cytokines
Dinoprostone
Interleukin-1beta
Interleukin-6
Peptide Hydrolases
Rheumatoid Factor
Tumor Necrosis Factor-alpha

Figure

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  Figure 1 The role of Th17 cell in the pathogenesis of rheumatoid arthritis. IL-17 produced by Th17 cell influences various kinds of cells and is involved in the development of inflammation, cartilage and bone loss, which are characteristics of rheumatoid arthritis. Abbreviations: MCP-1, Monocyte chemotactic peptide-1; GRO-α, Growth regulated protein-α; MMPs, Matrix metalloproteinases; NO, Nitric oxide; RANKL, Receptor Activator for Nuclear Factor κB Ligand.

• 

  Figure 2 Cytokine network in rheumatoid arthritis as a background for anticytokine therapy. Abbreviations: Blys, B lymphocyte stimulator; APRIL, A proliferation-inducing ligand; MMP, Matrix metalloproteinase; RANKL, Receptor Activator for Nuclear Factor κB Ligand; RANTES, Regulated on activation, normal T cell expressed and secreted

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