HLA-A and HLA-B Genotyping

HLA-A and HLA-B (major histocompatibility complex, class I, A, and B) are closely related proteins in the human leukocyte antigen (HLA) complex. They play major roles in the immune system and are found on nearly every cell.

Carriers of certain polymorphisms, such as HLA-A*31:01, HLA-B*15:02, HLA-B*57:01 rs2395029 (LD), and HLA-B*58:01, are at risk for severe hypersensitivity when given certain medications, including abacavir (Ziagen®), allopurinol (Zyloprim®), phenytoin (Dilantin®), and carbamazepine (Tegretol®).

These medications are typically used as part of treatments for epilepsy, bipolar disorder, gout, and HIV.[50]

Indications for HLA-A and HLA-B Testing

Testing prior to initiating commonly impacted drugs helps to identify patients at high risk for severe drug-induced hypersensitivity reactions. Testing should be considered for individuals with a personal or family history of adverse drug effects to abacavir (Ziagen®), allopurinol (Zyloprim®), and carbamazepine (Tegretol®). Testing should be done to confirm the presence of genotypes that affect the sensitivity to specific medications.

Patients initiating carbamazepine therapy may benefit from HLA-A*3101 testing. All patients of Asian ethnicity should be tested for the HLA-B*15:02 allele prior to phenytoin (Dilantin®), and carbamazepine (Tegretol®).  and fosphenytoin (Cerebyx®) administration. Patients of all ethnicities should be tested for HLA-B*57:01 rs2395029 (LD) prior to abacavir administration due to incidence of hypersensitivity. All patients should be tested for HLA-B*58:01 prior to allopurinol therapy due to severe cutaneous reactions.[51] Assessment of medical necessity for testing is up to the provider’s clinical judgment.