HLA-B58:01

Detailed article on HLA-B58:01

HLA-B58:01 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 serotype and is associated with certain drug hypersensitivity reactions, particularly to the medication allopurinol.

Structure and Function

The HLA-B58:01 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 recognition of these peptides by T cells is crucial for the immune system to distinguish between self and non-self, and to mount an appropriate immune response.

Genetic Variation

HLA-B58:01 is one of many alleles in the HLA-B locus, which is located on chromosome 6. The HLA-B locus is highly polymorphic, meaning there is a great deal of genetic variation, which allows for a wide range of peptide presentation and immune responses among different individuals.

Clinical Significance

HLA-B58:01 is most notably associated with an increased risk of severe cutaneous adverse reactions (SCARs) to allopurinol, a medication commonly used to treat gout and hyperuricemia. These reactions can include Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are life-threatening conditions characterized by widespread skin detachment and mucosal involvement.

Allopurinol Hypersensitivity

Individuals who carry the HLA-B58:01 allele are at a significantly higher risk of developing allopurinol-induced SCARs. As a result, genetic testing for HLA-B58:01 is recommended before initiating allopurinol therapy, especially in populations with a high prevalence of this allele, such as those of Han Chinese, Thai, and Korean descent.

Epidemiology

The frequency of the HLA-B58:01 allele varies among different ethnic groups. It is relatively common in Asian populations, with a prevalence of approximately 6-8% in Han Chinese, but is less common in European and African populations.

Testing and Prevention

Genetic testing for HLA-B58:01 can be performed using various methods, including polymerase chain reaction (PCR) and sequencing techniques. Identifying individuals with this allele can help prevent adverse drug reactions by guiding the choice of alternative medications.

Also see

• HLA-B
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Allopurinol
• Pharmacogenomics