Etiology of Ankylosing Spondylitis
The precise cause of ankylosing spondylitis (AS) is unknown, although there is evidence that genetic, individual host, infectious agents, and environmental factors may play a role. In this section, genetic predisposition, immunoregulatory (individual host) abnormalities, and environmental factors will be explored. The possible theory is that one of the factors or a combination of these factors, in addition to currently unidentified elements, may lead to the development of AS.
Human leukocyte antigen (HLA) associations have been implicated in the occurrence of several autoimmune conditions. One of the strongest of these is the association between HLA-B27 and AS. As seen in Fig.3115, the HLA-B27 is present in a large portion of the world. Currently, the pathogenesis of AS has attempted to include HLA-B27 into mechanistic models. The arthritogenic peptide theory states that HLA-B27 may bind to unique peptides of microbial or self-origin and present them to CD8+ T cells triggering AS.11548 The molecular mimicry theory states two possibilities may occur. The first possibility is that in its original form, the molecular mimicry that occurs between bacterial organisms and B27 was thought to cause misrecognition of B27-carrying tissues as foreign invaders. This would result in a humoral or cellular immune response against self-antigens. The second possibility was molecular mimicry occurred with bacterial and B27-presented endogenous peptides which then would elicit an autoimmune response. Additional theories include possible HLA-B27 misfolding and a link between HLA-B27 and infections.12455
Figure 3115 – Schematic and Approximate Representation of HLA-B27 Frequency Distribution Among World Populations
Figure 1, Page 399, Autoimmun Rev. 2008;7(5) is used with permission of Elsevier Inc. All rights reserved.
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Infectious agents with respect to host immune response have been considered as a potential development for AS. Bacterial organisms such as Klebsiella pneumoniae (commonly found in the gut), Streptococcus pyogenes, and Candida albicans have been suspected.11453 It is possible that the presence of HLA-B27 may cross-react with antigens found in K pneumoniae. AS may develop as a result of the antigenic components of infectious agents from the cross-reactivity or the resemblance to HLA. Following the production of antibacterial antibodies, they may bind to HLA molecules resulting in the activation of a complement cascade. This activation may lead to the inflammation and symptoms of the disease. Additionally, the bacterial antigens have been isolated from various AS joints.11549 However, attempts to confirm these findings have not been successful.11453
Role of Tumor Necrosis Factor-α in Ankylosing Spondylitis
The exact of role of tumor necrosis factor-α (TNF-α) in AS has yet to be defined. TNF-α is a naturally occurring cytokine secreted mainly by macrophages, monocytes, activated endothelial cells, fibroblasts, and chondrocytes.12461 Its actions include:
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Promotes inflammatory cytokines (interleukin [IL]-1, IL-6, and IL-8)
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Stimulates fibroblasts to express adhesion molecules
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Increases the transport of leukocytes into the inflammatory site
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Triggers the release of enzymes that damage cartilage and promote bone destruction
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Plays a role in sustaining the immune response
The continual emergence of new data on the pathophysiology of AS and the mechanism of the inflammatory process may help to confirm the exact role of TNF-α in AS.12462, 12463
Content on this page was last reviewed on January 01, 2010.
Content on this page was last changed on April 01, 2010.
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| 11505. | Mathieu A, Cauli A, Fiorillo MT, Sorrentino R. HLA-B27 and ankylosing spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis. Autoimmun Rev. 2008;7(5):398-403. |
| 11548. | Kim TH, Uhm WS, Inman RD. Pathogenesis of ankylosing spondylitis and reactive arthritis. Curr Opin Rheumatol. 2005;17(4):400-405. |
| 11549. | Ebringer A, Wilson C. HLA molecules, bacteria and autoimmunity. J Med Microbiol. 2000;49(4):305-311. |
| 12455. | Tsai WC. The Role of HLA-B27 in the Pathogenesis of Ankylosing Spondylitis. Current Rheumatology Reviews . 2008; 4: 99-102 |
| 12461. | Davis Jr JC. Understanding the Role of Tumor Necrosis Factor Inhibition in Ankylosing Spondylitis. Semin Arthritis Rheum . 2004;34:668-677. |
| 12462. | Sonel B, Tutkak H, Düzgün N. Serum levels of IL-1 beta, TNF-alpha, IL-8, and acute phase proteins in seronegative spondyloarthropathies. Joint Bone Spine . 2002;69(5):463-7. |
| 12463. | Keller C, Webb A, Davis J. Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review. Ann Rheum Dis . 2003;62(12):1128-32. |
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