Abstract
Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives.
Highlights
The major histocompatibility complex (MHC) is a group of cell surface proteins that play a pivotal role in T-cell activation because this process mandatorily requires that theT-cell receptor (TCR) engages with the complementary antigenic peptide bound to MHC molecules
Human leukocyte antigen (HLA) class I molecules are encoded by three loci known as classical HLA-A, HLA-B, and HLA-C genes while HLA class II molecules are encoded by classical HLA-DR, HLA-DQ, HLA-DP genes
HLA class I molecules are expressed by virtually all nucleated cells and present peptides derived from intracellularly expressed proteins to cytotoxic T cells (CD8+)
Summary
The major histocompatibility complex (MHC) is a group of cell surface proteins that play a pivotal role in T-cell activation because this process mandatorily requires that the. T-cell receptor (TCR) engages with the complementary antigenic peptide bound to MHC molecules. MHC is known as human leukocyte antigen (HLA). The HLA antigens are classified into two clusters HLA class I molecules are encoded by three loci known as classical HLA-A, HLA-B, and HLA-C genes while HLA class II molecules are encoded by classical HLA-DR, HLA-DQ, HLA-DP genes. HLA class I molecules are expressed by virtually all nucleated cells and present peptides derived from intracellularly expressed proteins to cytotoxic T cells (CD8+)
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