What is the significance of HLA-B27 (Human Leukocyte Antigen B27)?

From the Guidelines

HLA-B27 testing is recommended as a screening parameter for axial spondyloarthritis (axSpA) in patients with chronic low back pain, particularly those with inflammatory back pain, due to its high sensitivity and specificity, as shown in a study published in the Journal of the American College of Radiology in 2021 1. The presence of HLA-B27 is a significant risk factor for developing axSpA, and testing for this marker can help identify patients who may benefit from further evaluation and treatment. Some key points to consider when evaluating patients with suspected axSpA include:

• The presence of inflammatory back pain, which is characterized by insidious onset, improvement with exercise, and worsening with rest
• The age of onset, with axSpA typically presenting before the age of 45
• The presence of other clinical or imaging parameters, such as sacroiliitis or spondylitis, which can increase the pretest likelihood of axSpA
• The use of imaging modalities, such as MRI, to evaluate the sacroiliac joints and spine for signs of inflammation or damage According to a study published in the Annals of the Rheumatic Diseases in 2005, HLA-B27 testing has a higher sensitivity and specificity than inflammatory back pain for screening for axSpA, and is a useful tool for identifying patients who may benefit from further evaluation and treatment 1. Additionally, a study published in Arthritis Care & Research in 2019 recommends the use of HLA-B27 testing as part of a comprehensive treatment plan for axSpA, which includes NSAIDs, physical therapy, and biologic medications like TNF inhibitors or IL-17 inhibitors 1. Overall, HLA-B27 testing is a valuable tool for identifying patients with axSpA and guiding treatment decisions, and should be considered in patients with chronic low back pain and suspected axSpA.

From the Research

HLA B27 Overview

• HLA B27 is a member of the HLA class I family of genes in the major histocompatibility complex, with a prevalence of about 8% in the mid-European population 2.
• The association of HLA B27 alleles with ankylosing spondylitis (AS) was discovered 50 years ago, and HLA B27 explains less than 30% of the total genetic load 2.
• About 60%-90% of axSpA patients worldwide carry HLA B27, and the prevalence of the disease is linked to the frequency of HLA B27 in the population 2.

HLA B27 and Ankylosing Spondylitis

• HLA B27 is strongly associated with ankylosing spondylitis (AS), but the pathogenic role of HLA B27 is unknown 3.
• The arthritogenic peptide hypothesis proposes that HLA B27 presents peptides derived from exogenous sources such as bacteria to CD8 lymphocytes, which subsequently cross-react with antigens at the site of inflammation of the disease, causing inflammation 4.
• Studies have shown that HLA B27-positive patients with AS have higher family aggregation and an earlier onset of disease compared to those who are HLA B27 negative 5.

Clinical Features of HLA B27-Associated Ankylosing Spondylitis

• HLA B27-negative patients with AS present with statistically higher disease activity and functional impairment scores, as well as a higher prevalence of arthritis, dactylitis, and extra-articular manifestations such as psoriasis and inflammatory bowel disease 5.
• A meta-analysis found that HLA B27, HLA B2702, and HLA B2704 were positively associated with AS, and that HLA B27 was also associated with male sex, family history, uveitis, peripheral joint involvement, and hip joint involvement 6.

Mechanism of HLA B27 in Ankylosing Spondylitis

• The canonical function of HLA B27 is to present antigenic peptides to CD8 lymphocytes, leading to adaptive immune responses 4.
• Studies have shown that expansion of a restricted pool of CD8 lymphocytes is found in most AS patients, yet only in a small proportion of healthy HLA B27 carriers, supporting the theory that AS is driven by presentation of antigenic peptides to the adaptive immune system by HLA B27 4.