HLA-restricted Biology of Severe Cutaneous Adverse Reactions (SCARs): Dapsone-induced Hypersensitivity as an Example
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HLA proteins are pivotal in antigen processing and adaptive immunity. This study investigates the differential expression of class I and II HLAs in human skin, focusing on HLA-B’s role in drug-induced hypersensitivity syndromes (SCARs). Using RNA expression data from the Human Protein Atlas, we identified HLA-B as the highest expressed class I protein in exposed and non-exposed skin, with significant gender– and age-related variations. Male individuals exhibited higher HLA expression in sun-exposed skin, particularly for HLA-B, which aligns with reported higher SCAR incidences in males. Expression levels increased with age, suggesting a potential link to the heightened SCAR prevalence in older populations. Additionally, molecular docking analyses were performed to investigate HLA alleles associated with dapsone hypersensitivity. Using SWISS DOCK and AutoDock Vina, we identified four non-HLA-B13:01 alleles—B13:13, B40:01, B40:10, and B15:25—with significant binding potential, potentially explaining hypersensitivity cases not attributed to HLA-B13:01. These findings offer insights into the molecular basis of hypersensitivity syndromes and the epidemiological variability across populations.
