HLAs: Key regulators of T ‐cell‐mediated drug hypersensitivity

Adverse drug reactions (ADR) can be broadly categorised as either on‐target or off‐target. On‐target ADRs arise as a direct consequence of the pharmacological properties of the drug and are therefore predictable and dose‐dependent. On‐target ADRs comprise the majority (>80%) of ADRs, relate to the drug's interaction with its known pharmacological target and are a result of a complex interplay of genetic and ecologic factors. In contrast, off‐target ADRs, including immune‐mediated ADRs (IM‐ADRs), are due to unintended pharmacological interactions such as inadvertent ligation of host cell receptors or non‐pharmacological interactions mediated through an adaptive immune response. IM‐ADRs can be classified according to the primary immune cell involved and include B‐cell‐mediated (Gell‐Coombs type I‐III reactions) and T‐cell‐mediated (Gell‐Coombs type IV or delayed hypersensitivity) reactions. IM‐ADRs mediated by T cells are associated with phenotypically distinct clinical diagnoses and can vary from a mild delayed rash to a life‐threatening cutaneous, systemic or organ disease, such as Stephen Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms and drug‐induced liver disease. T‐cell‐mediated ADRs are strongly linked to the carriage of particular HLA risk alleles which are in the case of abacavir hypersensitivity and HLA‐B*57:01 has led to translation into the clinic as a routine screen...
Source: Tissue Antigens - Category: Allergy & Immunology Authors: Tags: REVIEW ARTICLE Source Type: research