HLA-B57:01

HLA-B57:01 is a specific allele of the human leukocyte antigen (HLA) system, which plays a critical role in the immune system by presenting peptides to T cells. This allele is part of the HLA-B gene locus, located on chromosome 6, and is known for its association with drug hypersensitivity reactions, particularly to the antiretroviral drug abacavir.

Structure and Function

The HLA-B57:01 allele encodes a protein that is part of the major histocompatibility complex (MHC) class I molecules. These molecules are expressed on the surface of almost all nucleated cells and are responsible for presenting endogenous peptides to CD8+ T cells. The structure of HLA-B57:01 includes a heavy chain that is non-covalently associated with β2-microglobulin. The peptide-binding groove of HLA-B57:01 has a unique conformation that influences its peptide-binding repertoire.

Clinical Significance

HLA-B57:01 is most notably associated with hypersensitivity to the drug abacavir, which is used in the treatment of HIV/AIDS. Individuals carrying this allele are at a significantly increased risk of developing abacavir hypersensitivity syndrome, a potentially life-threatening condition characterized by fever, rash, gastrointestinal symptoms, and respiratory distress. As a result, genetic screening for HLA-B57:01 is recommended before initiating abacavir therapy.

Abacavir Hypersensitivity

The mechanism of abacavir hypersensitivity involves the binding of abacavir to the peptide-binding groove of HLA-B57:01, altering the repertoire of peptides presented to T cells. This alteration triggers an inappropriate immune response, leading to the symptoms of hypersensitivity. The strong association between HLA-B57:01 and abacavir hypersensitivity has made it a model for understanding drug-induced hypersensitivity reactions.

Population Genetics

The frequency of the HLA-B57:01 allele varies among different populations. It is more prevalent in individuals of European descent and less common in Asian and African populations. This variation in allele frequency has implications for the risk of abacavir hypersensitivity in different ethnic groups.

Testing and Screening

Genetic testing for HLA-B57:01 is performed using various molecular techniques, including PCR-based methods and next-generation sequencing. The presence of the allele is a contraindication for the use of abacavir, and alternative antiretroviral therapies should be considered for individuals who test positive.

Research and Future Directions

Ongoing research is focused on understanding the structural basis of HLA-B57:01's interaction with abacavir and other drugs, as well as exploring the role of this allele in other immune-mediated conditions. Advances in personalized medicine and pharmacogenomics continue to highlight the importance of HLA typing in clinical practice.

Also see

• HLA-B
• Major histocompatibility complex
• Pharmacogenomics
• Drug hypersensitivity
• Abacavir