From the Guidelines
HLA-B27 is a significant genetic marker associated with an increased risk of developing certain autoimmune conditions, particularly ankylosing spondylitis and other spondyloarthropathies, with a strong association found in 74% to 89% of patients with axial spondyloarthritis 1. The presence of HLA-B27 is a key factor in the diagnosis of axial spondyloarthritis, and its testing is used as a diagnostic tool when evaluating patients with symptoms such as chronic lower back pain, sacroiliitis, or other inflammatory joint conditions.
- HLA-B27 testing is most valuable when combined with clinical symptoms and imaging studies for proper diagnosis.
- A positive HLA-B27 test does not definitively diagnose disease but indicates increased susceptibility, with many people with this marker never developing related conditions.
- The significance of HLA-B27 lies in its role in immune function, where it appears to affect how the body recognizes and responds to certain proteins, with current theories suggesting that HLA-B27 may present peptides to immune cells in a way that triggers autoimmune responses, or that the protein itself may fold incorrectly, causing cellular stress responses that lead to inflammation 1.
- Referral to a rheumatologist should be made for patients suspected of having axial spondyloarthritis who have had back pain since before 45 years of age that has lasted more than three months if they also have at least four of the following criteria, including a positive HLA-B27 test 1.
- Spondyloarthritis should not be ruled out based only on negative laboratory results from HLA-B27, C-reactive protein measurement, or erythrocyte sedimentation rate testing, and all patients diagnosed with axial spondyloarthritis should be referred to a subspecialist for a structured exercise program 1.
From the Research
Significance of HLA-B27
The Human Leukocyte Antigen B27 (HLA-B27) is a significant factor in the diagnosis and treatment of axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS). Some key points about HLA-B27 include:
- HLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but its effect on axial spondyloarthritis is apparently the opposite, with HLA-B27 positive subjects having less active spondyloarthritis compared to HLA-B27 negative subjects 2
- HLA-B27 is a predictor of effectiveness of treatment with TNF inhibitors in axial spondyloarthritis, with HLA-B27 positive patients having a lower risk of drug discontinuation compared to HLA-B27 negative patients 3
- HLA-B27 explains less than 30% of the total genetic load of ankylosing spondylitis, and its prevalence in the population is linked to the frequency of the disease 4
- The frequency of HLA-B27 varies around the world, and in an Argentinian cohort of axial spondyloarthritis patients, it was found to be 43%, with HLA-B27 positive patients having an earlier age of onset and more extra-articular features 5
Role of HLA-B27 in Disease Pathogenesis
The exact role of HLA-B27 in the pathogenesis of spondyloarthropathies is still unknown, but several hypotheses have been proposed, including:
- The peptide-presenting specificity of HLA-B27, which could trigger T-cell autoimmunity against a self-ligand of HLA-B27 elicited by a cross-reactive foreign antigen 6
- The slow folding and tendency to misfold of HLA-B27, which could trigger disease through activation of inflammatory pathways following induction of endoplasmic reticulum stress 6
- The capacity of HLA-B27 to form covalent heavy chain homodimers, which could be involved in disease through immunomodulation of both innate and adaptive responses to arthritogenic pathogens 6
Diagnostic and Prognostic Value of HLA-B27
HLA-B27 has a good specificity but low sensitivity for the diagnosis of axial spondyloarthritis, and its presence can facilitate the diagnosis of the disease, especially in patients with mild back pain 2, 5
- HLA-B27 can also be used as a predictor of treatment response, with HLA-B27 positive patients being more likely to respond to TNF inhibitors 3