What Are the Clinical Implications of HLA-B27 Positivity in Ankylosing Spondylitis?


Findings from the most extensive study to analyze the association between HLA-B27 status and manifestations of AS.

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Spanish researchers discovered that HLA-B27 positivity in ankylosing spondylitis is associated with earlier disease onset and higher family aggregation in white patients, while negativity is linked to more peripheral arthritis, dactylitis, and extra-articular disease.

Ankylosing spondylitis and HLA-B27
Axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS), is known to be associated with HLA-B27. However, up to 20% of patients with diagnosed AS do not carry HLA-B27.

Few studies have looked at HLA-B27 positivity in relation to AS, which often strikes patients in early adulthood and leads to severe disability if not treated effectively. Arévalo and colleagues1 sought to evaluate the influence of HLA-B27 on clinical expression in patients with AS.

The study
The researchers conducted a comparative, cross-sectional study using patients with AS from the REGISPONSER Spanish registry. Clinical and biological variables included age, sex, HLA-B27 status, disease onset, disease duration, diagnostic delay, axial symptoms, peripheral involvement, disease activity, and clinical disability as well as inflammatory markers and any other inflammatory involvement. Disease activity was assessed with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and clinical disability with the Bath Ankylosing Spondylitis Functional Index (BASFI). Ultimately, 1235 patients were included in the final analysis.

Next: the results and take-home points for clinicians

The results
• 83.3% of subjects were HLA-B27 positive.

• HLA-B27–positive subjects had a higher family aggregation (P = .002) and were of younger age (P = .012) and younger age at symptom onset (P < .001) and at diagnosis (P < .001) than HLA-B27–negative patients.

• HLA-B27–negative patients exhibited a higher disease activity measured by BASDAI (P = 0.047) and higher clinical disability measured by BASFI than HLA-B27–positive patients.

• HLA-B27–negative patients had a higher prevalence of peripheral arthritis (P = .023), dactylitis (P = .001), and extra-articular manifestations, especially psoriasis (P < .001) and inflammatory bowel disease (P < .001).

• No differences were observed between groups for biological markers of inflammation (erythrocyte sedimentation rate and C-reactive protein level) or structural damage.

Take-home points
• Clinicians should be vigilant for HLA-B27 positivity in patients who present with AS earlier and may even consider screening family members with known phenotypic positivity, since family aggregation is greater.

• HLA-B27–negative patients with AS should be monitored for peripheral involvement, psoriasis, and inflammatory bowel disease.

• Patients with AS can be reassured that HLA-B27 positivity does not increase the extent of axial structural damage or disease burden.


1. Arévalo M, Gratacós Masmitjà J, Moreno M, et al; REGISPONSER group. Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the REGISPONSER database. Arthritis Res Ther. 2018;20:221. doi: 10.1186/s13075-018-1724-7.

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