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HLA B27

HLA-B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC). HLA-B27 is present in 1% of Asians, 3-4% of African-Americans, and 6-8% of Caucasians. HLA-B27 is found in 74 to 89% of patients with either nonradiographic axial spondyloarthritis or ankylosing spondylitis. When HLA-B27 is present, the odds ratio for developing disease is >50. The absolute risk of spondyloarthritis in persons with HLA-B27 positivity is estimated to be 2 to 10% but is higher if a first-degree relative is affected.

More than 140 variant alleles of HLA-B27 have been described. Associations with ankylosing spondylitis are firmly established for subtypes B*27:02 (Mediterranean populations), B*27:04 (Far Eastern populations), B*27:05 (white and worldwide populations), and B*27:07 (South Asian and Middle Eastern populations.). Subtypes B*27:06 (Southeast Asian populations) and B*27:09 (southern Italian and Sardinian populations) are not associated with ankylosing spondylitis. The basis for the association between HLA-B27 and axial spondyloarthritis and ankylosing spondylitis is unknown.

In 2009, the Assessment of SpondyloArthritis International Society (ASAS) formulated classification criteria for axial spondyloarthritis that were based on imaging, clinical, and laboratory criteria. Diagnosis is established in persons who have had back pain for 3 or more consecutive months before reaching 45 years of age, who have had the presence of sacroiliitis confirmed on MRI or plain radiography, and who have at least one clinical or laboratory finding that is characteristic of spondyloarthritis. Alternatively, persons with this history who have a positive test result for HLA-B27 plus two features of spondyloarthritis as detected on clinical examination or laboratory analysis also fulfill the criteria for a diagnosis of axial spondyloarthritis.

Laboratory findings in ankylosing spondylitis include an elevated erythrocyte sedimentation rate and elevated C-reactive protein in approximately 50 to 70 percent of patients with active disease. Normochromic normocytic anemia is occasionally seen. Serum bone-specific alkaline phosphatase may be elevated in severe disease. Serum levels of immunoglobulin A (IgA) are also commonly elevated. Synovial fluid examination usually shows acute inflammation with increased polymorphonuclear leukocytes.

HLA-B27 is present in 79% of patients with Reiter’s syndrome, psoriatic arthritis and 42% of patients with juvenile rheumatoid arthritis.  It has also been linked with congenital deficiency of complement components C2 and C4, adrenal hyperplasia, and inflammatory bowel disease. The presence of HLA-B27 in these disorders is not diagnostic.

HLA-B27 is detected by staining T lymphocytes with anti-HLA27 antibody that is fluorescently labeled. Specimen requirement is a lavender top (EDTA) tube of blood stored at room temperature.

Reference value is negative.

Taurog JD et al. Ankylosing Spondylitis and Axial Spondyloarthritis N Engl J Med 2016; 374:2563-2574.

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