Association between HLA alleles and adverse drug reactions. Mechanisms involved

Introduction Adverse drug reactions (ADRs) represent a major public health problem. A significant subset of these reactions, particularly delayed-type hypersensitivity reactions and severe cutaneous adverse reactions (SCARs), show a strong association with specific alleles of the human major histocompatibility complex (HLA). The following review aims to summarize the current evidence on the associations between HLA alleles and ADR, covering both well-established associations and those with emerging evidence. The proposed immunological mechanisms for these adverse reactions are also outlined, including hapten/pro-hapten, pharmacological interaction with immune receptors (p-i) and the altered peptide models. Content A systematic literature search was conducted in the PubMed database (MEDLINE) through April 2025, independently by the authors. A consensus was then reached, with a total of 56 articles being used in this review. Summary A division by groups of drugs is established (antiretrovirals, aromatic antiepileptics, allopurinol, antibiotics and other drugs), indicating for each of them the HLA involved, the proposed mechanism, ethnicity in which the association was described and the degree of association. A table is included to facilitate consultation of key information. Outlook HLA alleles play a critical role in the pathogenesis of numerous ADRs, and further studies are needed to clarify HLA-ADRs associations and the mechanisms involved.