Quiz on human leukocyte antigen (HLA) B 27

Acute anterior uveitis is a common extra-articular manifestation of HLA-B27-related spondyloarthropathies

Flow cytometry is the most commonly used method in clinical laboratories for detecting HLA-B27 on the surface of lymphocytes via monoclonal antibodies. PCR is also widely used to detect HLA-B27 at the DNA level, particularly as a confirmatory test or for detailed typing. Both techniques are accurate and standard approaches for HLA-B27 detection. 

One prevailing theory is that HLA-B27 presents specific peptides to CD8+ T lymphocytes, possibly leading to autoimmunity through cross-reactivity with self-antigens (“arthritogenic peptide hypothesis 

Misfolding and dimerization of the HLA-B27 molecule may result in unusual immune responses, leading to inflammation and autoimmunity, another proposed mechanism in the pathogenesis of HLA-B27-associated diseases.

While HLA-B27 positivity is not sufficient for diagnosis, it is a useful tool in diagnosing spondyloarthropathies and understanding prognosis, especially when clinical signs are ambiguous. 

HLA-B27 positivity increases the risk of ankylosing spondylitis by up to 87 times compared to non-carriers, highlighting the gene’s significant role in disease susceptibility. 

The misfolding, dimerization, and arthritogenic peptide hypotheses all explain different ways HLA-B27 may trigger immune responses and contribute to arthritis. In contrast, the immune checkpoint inhibition hypothesis is unrelated to HLA-B27’s role in these immune mechanisms and primarily concerns immune regulation in other contexts. 

Rheumatoid arthritis (RA) is not associated with HLA-B27. It is typically linked with HLA-DR4 and HLA-DR1. HLA-B27 is associated with seronegative spondyloarthropathies, such as ankylosing spondylitis, reactive arthritis, and uveitis. 

Approximately 60–90% of individuals with axial spondyloarthritis, including ankylosing spondylitis, carry the HLA-B27 gene, making it a strong diagnostic marker, although not every HLA-B27 carrier develops the disease. 

The 1973 discovery by Schlosstein and Brewerton marked a paradigm shift in immunogenetics. It was the first time a specific HLA allele (HLA-B27) was shown to be strongly associated with a complex autoimmune disease, ankylosing spondylitis. This paved the way for understanding genetic predispositions in autoimmune and inflammatory conditions.