Blood Testing for Ankylosing Spondylitis
The primary blood test for ankylosing spondylitis is HLA-B27, which is positive in 74-89% of patients with axial spondyloarthritis, but it should be used as a screening parameter rather than a definitive diagnostic test and must be combined with clinical criteria. 1, 2
Primary Blood Tests
HLA-B27 Testing
- HLA-B27 is the strongest genetic marker associated with ankylosing spondylitis and is present in 80-95% of AS patients 2, 3
- The test only needs to be performed once in a patient's lifetime using molecular methods that detect the HLA-B27 genotype directly 2
- Approximately 30-40% of patients with chronic back pain and positive HLA-B27 will ultimately receive an AS diagnosis 1, 2
Inflammatory Markers
- C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are the other clinically relevant blood tests, though they are non-specific and can be normal even in active disease 2
- These markers provide supporting evidence but should not be used to rule out the diagnosis if normal 4, 2
Critical Diagnostic Pitfalls
What NOT to Do
- Never rule out spondyloarthritis based solely on negative HLA-B27, normal CRP, or normal ESR 4, 1, 2
- Approximately 10% of AS cases are HLA-B27 negative, meaning the disease can absolutely occur without this marker 2
- Do not use HLA-B27 testing early in the diagnostic approach before establishing clinical suspicion with inflammatory back pain characteristics 1
Proper Test Interpretation
- HLA-B27 positivity increases the likelihood of peripheral spondyloarthritis but does not confirm the diagnosis 4, 1
- All three markers (HLA-B27, CRP, ESR) must be interpreted within the clinical context of inflammatory back pain, imaging findings, and extra-articular manifestations 2
- The test provides a probability statement rather than absolute confirmation or exclusion of disease 5
When to Order HLA-B27
Order HLA-B27 testing when the patient has:
- Chronic back pain lasting more than 3 months with onset before age 45 1
- At least three of the following clinical criteria: back pain before age 35, waking at night due to pain, buttock pain, improvement with exercise or within 2 days of NSAID use, first-degree relative with spondyloarthritis, or current/previous arthritis, enthesitis, or psoriasis 4, 1
If HLA-B27 is positive AND the patient meets at least three clinical criteria, refer to rheumatology 4, 1
Clinical Context Matters
- HLA-B27 negative patients tend to have later disease onset (average 27.7 years vs 24.8 years in HLA-B27 positive patients) and longer diagnostic delays (11.4 years vs 8.5 years) 6
- Acute anterior uveitis is significantly less frequent in HLA-B27 negative patients (26%) compared to HLA-B27 positive patients (41%) 6
- In IBD-associated AS, HLA-B27 prevalence is lower (25-75%), making it less reliable in this population 2