Asymptomatic Rate in HLA-B27 Positive Individuals
Approximately 75% of HLA-B27 positive individuals will remain asymptomatic and never develop spondyloarthropathy throughout their lifetime. 1
Key Epidemiologic Data
The most robust long-term cohort data demonstrates that only about 25% of HLA-B27 positive individuals will develop spondyloarthropathy over their lifetime, meaning the vast majority (75%) remain disease-free. 1 This finding is supported by multiple lines of evidence:
- Among HLA-B27 positive first-degree relatives of patients with axial spondyloarthropathy, approximately 25% developed the disease, while 75% remained asymptomatic. 1
- In the general population, only 1.3% of HLA-B27 positive individuals aged 45 years or older have ankylosing spondylitis, though this increases to 21% among first-degree relatives of AS patients. 2
- Population-based screening of blood donors found that 13.6% of HLA-B27 positive individuals had spondyloarthropathy compared to 0.7% of HLA-B27 negative subjects, yielding a relative risk of 20.7. 3
Clinical Context and Reassurance
HLA-B27 carriage does not adversely impact survival or health outcomes in individuals who do not develop spondyloarthropathy. 1 This provides important reassurance to the majority of HLA-B27 positive individuals who test positive during diagnostic evaluation but remain disease-free throughout life.
The prevalence of HLA-B27 in mid-European populations is approximately 8%, with about 60-90% of axial spondyloarthropathy patients worldwide carrying HLA-B27. 4 However, HLA-B27 explains less than 30% of the total genetic load for disease development, indicating that additional genetic and environmental factors are required for disease manifestation. 4
Why HLA-B27 Testing Is Not Used for Population Screening
Because 75% of HLA-B27 positive individuals never develop disease, HLA-B27 testing is not recommended as a standalone screening tool in the general population. 1 The test should only be used in appropriate clinical contexts:
- In patients with chronic back pain (>3 months) starting before age 45 with inflammatory characteristics. 5
- When combined with clinical criteria such as inflammatory back pain features (morning stiffness >30 minutes, nocturnal pain, improvement with exercise). 1
- HLA-B27 positivity in patients with chronic back pain raises the post-test probability of axial spondyloarthropathy to approximately 32%, meaning roughly 3 HLA-B27 positive patients with chronic back pain need evaluation to diagnose 1 case. 5
Predictive Features That Increase Risk
Among HLA-B27 positive individuals, certain features significantly increase the likelihood of developing disease:
- Acute anterior uveitis substantially increases risk (odds ratio: 4.7,95% CI: 2.2-10.5). 1
- Family history matters: HLA-B27 positive first-degree relatives of AS patients have a 16-fold greater risk compared to HLA-B27 positive individuals in the general population. 2
- Chronic inflammatory back pain at a young age was not found to be a reliable predictor of long-term disease development. 1
Important Caveats
- Approximately 10% of ankylosing spondylitis cases are HLA-B27 negative, so a negative test does not rule out disease. 5, 6
- Two HLA-B27 subtypes (B2706 in Southeast Asia and B2709 in Sardinia) are not associated with ankylosing spondylitis. 7
- HLA-B27 is found in only 25-75% of patients with inflammatory bowel disease-associated ankylosing spondylitis, making it less reliable in this population. 8, 5