New strategies to predict and prevent serious immunologically mediated adverse drug reactions.

NEW STRATEGIES TO PREDICT AND PREVENT SERIOUS IMMUNOLOGICALLY MEDIATED ADVERSE DRUG REACTIONS. Trans Am Clin Climatol Assoc. 2018;129:74-87 Authors: Phillips EJ Abstract Preventive efforts for serious immunologically mediated adverse drug reactions (IM-ADRs) have been fueled by discovery of strong class I human leukocyte antigen (HLA) associations; however, the low positive predictive value of HLA for IM-ADRs has limited translation. Studies were undertaken to explain why most patients carrying an HLA risk allele do not develop IM-ADR on exposure to the risk drug. Tissue-specific approaches defined the T-cell receptor (TCR) repertoire and phenotype of the pathogenic T cells found in the skin and blister fluid of IM-ADRs. Dominant CD8+ T cell clonotypes representing >50% of total TCRαβ sequences among CD8+ CD137+ T cells were identified in tissue to identify the pathogenic activated T cells. Identification of the specific molecular and cellular signatures of the antigen-driven pathogenic T cells will facilitate more specific mechanisms to determine the small percentage of individuals carrying an HLA risk allele who are likely to develop an IM-ADR before drug exposure. PMID: 30166701 [PubMed - in process]
Source: Transactions of the American Clinical and Climatological Association - Category: General Medicine Tags: Trans Am Clin Climatol Assoc Source Type: research