Ankylosing spondylitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Ankylosing spondylitis (AS), a spondyloarthropathy, is a chronic, multisystem inflammatory disorder involving primarily the sacroiliac (SI) joints and the axial skeleton. The outcome in patients with a spondyloarthropathy, including AS, is generally compared with that in patients with a disease such as rheumatoid arthritis.Mostly the joints where the spine joins the pelvis are also affected.Back pain is one of the most prominent symptoms of the ankylosing spondylitis (AS) which is intermittent in nature. Stiffness in the affected joints gets worse.It is believed that both the combination of genetic and environmental factors play an important role in the pathogenesis of ankylosing spondylitis (AS) and the underlying etiology is believed to be autoimmune or autoinflammatory.
Pathophysiology
Pathogenesis[1]
- It is understood that ankylosing spondylitis (AS) is the result of genetic and environmental factors.
- Ankylosing spondylitis (AS) is a chronic inflammatory disease that can affect sacroiliac joints and axial skeleton and cause significant functional and structural implications of the affected joints.
- Ankylosing spondylitis (AS) has a familial associations particularly among the patients who are positive for human leukocyte antigen (HLA)–B27 .
Genetics
- Genes involved in the pathogenesis of ankylosing spondylitis (AS) include Human Leukocyte Antigen–B27(HLA-B27).[2]
- The expression of HLA-B27 is more in the antigen presenting cells.
- HLA-B27 binds to b2 microglobulin after translation and tertiary folding and then loaded with an oligopeptide.
- The complex now passes via Golgi apparatus to the cell surface where the antigenic peptide is presented to either CD8+ lymphocytes or NK cells.[3]
- 90% of the time HLA B27 shows strong genetic association with AS, But only 5% of the patients who are positive for HLA B27 are going to develop ankylosing spondylitis (AS).
- HLA-B27 was found to have at least 25 allele subtypes which encode for 25 different gene products. Among all the 25 different alleles B*2705 is most common subtype which is thought to be a parent molecule and associated with higher risk of ankylosing spondylitis (AS).
- B*2701, B*2702, B*2704, and B*2707 are the other subtypes which confer disease susceptibility.[4]
- In peripheral blood mononuclear cells HLA–B27 has been found to be more highly expressed, than in healthy HLA-B27+ individuals. Furthermore, B*2705 expression levels were found to be higher in AS patients.[5]
- Many theories have been postulated with regard to the molecular pathogenesis role of HLA-B27 in AS which include arthritogenic peptides, aberrant folding, HLA-B27 misfolding, and increased intracellular microbial survival.[6]
HLA-B27 in the pathogenesis of ankylosing spondylitis
- Single amino acid changes from aspartate in the B*2705 allele to histidine in the B*2709 allele results in loss of the association with AS.[7][8]
| Hypothesis | Pathogenesis |
|---|---|
| Arthritogenic peptides | Immunological (adaptive immunity) |
| Heavy chain of aberrant surface | Immunological (innate immunity) |
| Abnormal protein folding | Intracellular (innate immunity) |
| Enhanced microbial survival | Intracellular (innate immunity) |
References
- ↑ Shamji, Mohammed F.; Bafaquh, Mohammed; Tsai, Eve (2008). "The pathogenesis of ankylosing spondylitis". Neurosurgical Focus. 24 (1): E3. doi:10.3171/FOC/2008/24/1/E3. ISSN 1092-0684.
- ↑ Fiorillo MT, Greco G, Maragno M, Potolicchio I, Monizio A, Dupuis ML, Sorrentino R (August 1998). "The naturally occurring polymorphism Asp116-->His116, differentiating the ankylosing spondylitis-associated HLA-B*2705 from the non-associated HLA-B*2709 subtype, influences peptide-specific CD8 T cell recognition". Eur. J. Immunol. 28 (8): 2508–16. PMID 9710228.
- ↑ Fiorillo MT, Greco G, Maragno M, Potolicchio I, Monizio A, Dupuis ML, Sorrentino R (August 1998). "The naturally occurring polymorphism Asp116-->His116, differentiating the ankylosing spondylitis-associated HLA-B*2705 from the non-associated HLA-B*2709 subtype, influences peptide-specific CD8 T cell recognition". Eur. J. Immunol. 28 (8): 2508–16. PMID 9710228.
- ↑ Hülsmeyer M, Fiorillo MT, Bettosini F, Sorrentino R, Saenger W, Ziegler A, Uchanska-Ziegler B (January 2004). "Dual, HLA-B27 subtype-dependent conformation of a self-peptide". J. Exp. Med. 199 (2): 271–81. doi:10.1084/jem.20031690. PMC 2211767. PMID 14734527.
- ↑ Benjamin R, Parham P (April 1990). "Guilt by association: HLA-B27 and ankylosing spondylitis". Immunol. Today. 11 (4): 137–42. PMID 2187471.
- ↑ Hülsmeyer M, Fiorillo MT, Bettosini F, Sorrentino R, Saenger W, Ziegler A, Uchanska-Ziegler B (January 2004). "Dual, HLA-B27 subtype-dependent conformation of a self-peptide". J. Exp. Med. 199 (2): 271–81. doi:10.1084/jem.20031690. PMC 2211767. PMID 14734527.
- ↑ Del Porto P, D'Amato M, Fiorillo MT, Tuosto L, Piccolella E, Sorrentino R (October 1994). "Identification of a novel HLA-B27 subtype by restriction analysis of a cytotoxic gamma delta T cell clone". J. Immunol. 153 (7): 3093–100. PMID 8089488.
- ↑ Hülsmeyer M, Fiorillo MT, Bettosini F, Sorrentino R, Saenger W, Ziegler A, Uchanska-Ziegler B (January 2004). "Dual, HLA-B27 subtype-dependent conformation of a self-peptide". J. Exp. Med. 199 (2): 271–81. doi:10.1084/jem.20031690. PMC 2211767. PMID 14734527.