What is HLA-B27 (Human Leukocyte Antigen B27)?

From the Guidelines

HLA-B27 is a genetic marker that plays a crucial role in the immune system and is strongly associated with several autoimmune conditions, including ankylosing spondylitis and axial spondyloarthritis, with approximately 74% to 89% of patients testing positive for this marker 1.

Definition and Clinical Significance

HLA-B27 is a protein encoded by a gene in the human leukocyte antigen (HLA) complex, which helps the immune system distinguish between the body's own cells and foreign invaders. This marker is clinically significant because it is strongly associated with several autoimmune conditions, particularly ankylosing spondylitis and axial spondyloarthritis.

Associated Conditions

Other conditions linked to this marker include reactive arthritis, psoriatic arthritis, inflammatory bowel disease-associated arthritis, and anterior uveitis.

Testing and Diagnosis

Testing for HLA-B27 is done through a simple blood test that looks for this specific protein on white blood cells. While having the HLA-B27 marker increases risk for these conditions, many people with the marker never develop disease, as environmental triggers and other genetic factors also play important roles in disease development.

Clinical Implications

The presence of HLA-B27 can help doctors make a diagnosis when symptoms are consistent with associated conditions, but it's not used as a screening test for the general population. According to the most recent study, the prevalence of axial spondyloarthritis is estimated to be between 0.9% to 1.4% in the United States adult population, and there is a strong association with HLA-B27, which is positive in 74% to 89% of patients 1. Some key points to consider:

• HLA-B27 is a genetic marker that plays a crucial role in the immune system
• It is strongly associated with several autoimmune conditions, including ankylosing spondylitis and axial spondyloarthritis
• Testing for HLA-B27 is done through a simple blood test
• The presence of HLA-B27 can help doctors make a diagnosis when symptoms are consistent with associated conditions
• It is not used as a screening test for the general population, as many people with the marker never develop disease.

From the Research

Definition of HLA-B27

• HLA-B27 is a member of the HLA class I family of genes in the major histocompatibility complex 2
• It is a human lymphocyte antigen whose name goes back to its discovery in studies of transplanted tissue compatibility 2
• HLA-B27 is strongly associated with ankylosing spondylitis (AS), a highly heritable disease, which is part of the spectrum of axial spondyloarthritis (axSpA) 2, 3

Function of HLA-B27

• The function of HLA class I molecules, including HLA-B27, is to present peptides to the immune system to defend the organism against microbes targeted by CD8+T cells 2
• HLA-B27 binds and presents peptides from influenza, HIV, Epstein-Barr virus, and other viruses, leading to vigorous and specific cytotoxic T lymphocyte responses 4
• HLA-B27 can also form disulfide-bonded homodimers, which are expressed on the cell surface and are ligands for a number of natural killer and related immunoreceptors 4

Disease Associations

• HLA-B27 is associated with ankylosing spondylitis (AS) and other spondyloarthritides 2, 3, 4
• The prevalence of AS is linked to the frequency of HLA-B27 in the population, with about 60%-90% of axSpA patients worldwide carrying HLA-B27 2
• HLA-B27-positive patients with AS may have an increased risk of malignancy, particularly if diagnosed after age 30 and requiring biologic therapy 5

Pathogenic Role

• The pathogenic role of HLA-B27 in AS is unknown, but two broad theories have been proposed: the arthritogenic peptide hypothesis and the theory that HLA-B27 can "behave badly" and lead to endoplasmic reticulum stress and autophagy responses 3
• The arthritogenic peptide hypothesis suggests that disease results from the ability of HLA-B27 to bind a unique peptide or a set of antigenic peptides 3, 4
• The role of ERAP1, an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules, has also been implicated in the pathogenesis of AS 6