HLA-B27: an immunogenetic marker of spondyloarthritis

The human leukocyte antigen (HLA) system presents peptide antigens to immune cells. HLA gene diversity helps the immune system recognize a broad range of antigens. Some HLA variants are associated with susceptibility to immune-mediated inflammatory diseases, but they are not the sole cause of those diseases.

HLA-B27 is an HLA-B variant strongly associated with axial spondyloarthritis, including ankylosing spondylitis, also known as Bechterew disease. It may also occur in reactive arthritis, some forms of psoriatic arthritis and inflammatory bowel disease-associated arthritis, and acute anterior uveitis. In children, the association is particularly relevant to enthesitis-related arthritis and juvenile spondyloarthritis; HLA-B27 is not a universal marker of all forms of juvenile idiopathic arthritis.

Spondyloarthritis can affect the spine, sacroiliac and peripheral joints, and tendon or ligament attachment sites. Extra-articular manifestations include uveitis, psoriasis and inflammatory bowel disease. The historical term “seronegative” reflects the usual absence of rheumatoid factor; absence of every autoantibody is not required for diagnosis.

The mechanisms linking HLA-B27 to disease remain under investigation. Molecular mimicry and altered antigen presentation are research hypotheses rather than a single proven mechanism. HLA-B27 frequency and the strength of its association with disease differ between populations and subtypes. A single relative-risk estimate or disease probability therefore cannot be applied to every individual.

What the result means

In someone with characteristic symptoms, a positive HLA-B27 result increases the likelihood of spondyloarthritis but cannot establish the diagnosis on its own. Most HLA-B27 carriers never develop ankylosing spondylitis. A negative result does not exclude spondyloarthritis, including axial disease.

A rheumatologist interprets the result alongside the pattern of back pain, arthritis, enthesitis, family history, extra-articular features, inflammatory markers and imaging. Normal C-reactive protein and ESR also do not exclude the disease. Sacroiliac joint radiographs and MRI may be used when appropriate.

When testing may help

• Suspected axial spondyloarthritis or ankylosing spondylitis.
• Clarifying peripheral spondyloarthritis, including reactive, psoriatic and inflammatory bowel disease-associated arthritis.
• Uveitis with features suggesting possible spondyloarthritis.
• Suspected juvenile spondyloarthritis or enthesitis-related arthritis, assessed by a pediatric rheumatologist.

The test is not intended for population screening of healthy people and does not determine treatment by itself. Eye pain, redness, light sensitivity or deterioration in vision requires urgent ophthalmological assessment.