Ankylosing apondylitis is associated with ?
**Core Concept**
Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis, spinal stiffness, and eventual fusion of vertebrae, leading to a loss of spinal mobility. The underlying pathophysiology involves an abnormal immune response, specifically an association with the human leukocyte antigen (HLA)-B27 gene.
**Why the Correct Answer is Right**
The association of AS with HLA-B27 is well-established, with approximately 90% of patients testing positive for this gene. The HLA-B27 molecule is a major histocompatibility complex (MHC) class I antigen, which presents peptides from endogenously synthesized proteins to CD8+ T cells. The immune response to these peptides leads to inflammation and tissue damage in AS. The genetic predisposition is thought to be linked to the ability of HLA-B27 to form a misfolded protein complex, which triggers an autoimmune response.
**Why Each Wrong Option is Incorrect**
**Option A:** HLA-A2 is not associated with ankylosing spondylitis. This MHC class I antigen is more commonly linked to certain viral infections and some cancers.
**Option B:** Rheumatoid factor is a marker of rheumatoid arthritis, not ankylosing spondylitis. While both conditions are autoimmune, they have distinct pathophysiologies and clinical presentations.
**Option C:** TNF-alpha is a pro-inflammatory cytokine involved in various autoimmune diseases, including AS. However, it is not the primary genetic association with AS.
**Clinical Pearl / High-Yield Fact**
Remember that HLA-B27 positivity is not specific to AS, as it can also be found in healthy individuals. However, in the context of AS, HLA-B27 positivity is a useful diagnostic clue and can help guide further investigation.
**Correct Answer: HLA-B27**