Spondyloarthropathy pathophysiology
Pathophysiology
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Spondyloarthropathies (SpA) is an inflammatory disease, which mainly affect the axial skeleton and peripheral joints same as other rheumatic disease but with different pathophysiology. there are two main processes that eventuate in symptoms of this disease:
- Inflammation of bone marrow or entheses
- This can cause pain and stiffness in affected joints
- Ankylosis (overgrowth of the bone)
- Eventuate in impaired function of the spine and reduction in range of motion of affected joints
Association of SpA with HLA-B27 gene have been known since 1973. In 95% of patients with Ankylosing spondylitis (AS) this allele is present, however, the reason why HLA-B27 is really strongly correlated to SpA is somehow uncleared.
There are some key points that can help to find the mechanism of SpA :
- SpA does not display the prototypical genetic, clinical and immunological features of T-cell and/or B-cell- mediated autoimmune diseases.
- B-cell and T-cell targeted therapies are not effective in SpA
- HLA-B27-dependent UPR leads to augmented IL-23 production, but the role of UPR in vivo remains to be investigated in more detail.
- Alternative macrophage polarization is a hallmark of SpA.
- Innate immune cells rather than T cells are the main producers of IL-17 in SpA.
The genetic responsibility in SpA have been discussed and is concluded in numerous studies, albeit, by the advent of new technological devices, HLA-B27 subtypes are known better than before.
In the table below association of some genes and their association in the specific type of SpA are described
| Overview of the gene, and their association in SpA | |
|---|---|
| HLA-B27 subtype | Association |
| HLA-B*2702 | Association with AS |
| HLA-B*2704 | Association with SpA |
| HLA-B*2705 | Strong association with AS |
| HLA-B*2706 | Very weak association with SpA |
| HLA-B*2709 | AS sparing |
Not only HLA-B gene are suspected for SpA, but also there are other genes that their association in presence of SpA are under investigation, which included:
- HLA-B (Associated with Ankylosing spondylitis )
- ERAP1 (Associated with Ankylosing spondylitis )
- IL23R (Associated with Ankylosing spondylitis )
- TNFRSF1A (Probably associated with Ankylosing spondylitis )
- TRADD (Probably associated with Ankylosing spondylitis )
- TNFRSF15 (Probably associated with Ankylosing spondylitis )
- IL1A (Probably associated with Ankylosing spondylitis )
- IL1R2 (Probably associated with Ankylosing spondylitis )
- CARD9 (Probably associated with Ankylosing spondylitis )
- ANTXR2 (Probably associated with Ankylosing spondylitis )