What does a positive Human Leukocyte Antigen B27 (HLA B27) test result mean?

From the Guidelines

A positive HLA-B27 test is a significant indicator of a potential autoimmune condition, particularly axial spondyloarthritis, but it does not definitively diagnose the disease, as approximately 74% to 89% of patients with axial spondyloarthritis are HLA-B27 positive, while many people with this marker remain asymptomatic 1.

Key Points to Consider

• The presence of HLA-B27 is strongly associated with axial spondyloarthritis, including ankylosing spondylitis, but it is not exclusive to these conditions 1.
• A positive HLA-B27 test, combined with symptoms such as chronic back pain, stiffness, and inflammatory markers, can aid in the diagnosis of axial spondyloarthritis 1.
• The HLA-B27 marker is found in about 8% of the general population, but its presence is significantly higher in individuals with certain autoimmune diseases, suggesting a genetic predisposition 1.
• The diagnosis of axial spondyloarthritis should be based on a combination of clinical presentation, imaging findings, and laboratory results, including but not limited to HLA-B27 testing 1.

Clinical Implications

• Patients with a positive HLA-B27 test and symptoms suggestive of axial spondyloarthritis should undergo further evaluation, including imaging studies and potentially MRI to assess for inflammatory changes in the sacroiliac joints and spine 1.
• Early diagnosis and treatment of axial spondyloarthritis can significantly improve quality of life and reduce disease activity, highlighting the importance of recognizing HLA-B27 as part of a broader diagnostic approach 1.
• Treatment algorithms for axial spondyloarthritis focus on controlling disease activity and improving quality of life, with biologic agents such as TNF-a antagonists being a standard of care for patients with active disease despite nonsteroidal anti-inflammatory drugs 1.

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 involved in presenting peptides to the immune system to defend the organism against microbes targeted by CD8+T cells 2

Association with Ankylosing Spondylitis

• HLA B27 is strongly associated with ankylosing spondylitis (AS), a highly heritable disease 2, 3
• About 60%-90% of axSpA patients worldwide carry HLA B27 2
• The presence of HLA B27 is related to an earlier disease onset and higher family aggregation in Caucasian AS patients 4

Clinical Features

• HLA B27-positive patients show higher family aggregation and an earlier onset of disease compared with those who are HLA B27 negative 4
• HLA B27-negative patients present statistically higher disease activity and functional impairment scores, and higher prevalence of arthritis, dactylitis, and extra-articular manifestations 4
• HLA B27 is associated with uveitis, peripheral joint involvement, and hip joints involvement in AS patients 3

Pathogenic Role

• The pathogenic role of HLA B27 is unknown, but two broad theories explain its role in AS pathogenesis: the presentation of antigenic peptides to cytotoxic T cells, and the misfolding of HLA B27 leading to endoplasmic reticulum stress and autophagy responses 5
• HLA B27 can also "behave badly" and lead to proinflammatory effects by binding to innate immune receptors on T, NK, and myeloid cells 5