Figure 1:
Classification of on-target and off-target ADRS Pink panel illustrates an example of an on-target ADR. Blue panel (left) illustrates non-immunologically-mediated off-target effects: direct cellular toxicity or disruption of normal physiology, interaction with non-immune receptors, and interaction with immune receptors (eg, non-IgE-mediated mast-cell activation via G-protein coupled receptors). Blue panel (right) shows immunologically mediated adaptive immune responses (antibody-mediated [eg, IgE] immediate reactions or T-cell-mediated delayed reactions). Predisposition to both on-target and off-target reactions is driven by genetic variation, but also ecological factors that can vary over the course of an individual’s lifetime. ADR=adverse drug reaction. Bid=BH3 interacting-domain death. C difficile=Clostridioides difficile. ER=endoplasmic reticulum. FcεR1=high-affinity IgE receptor. HSR=hypersensitivity reaction. MRGPRX2=MAS-related G-protein coupled receptor member X2. PKC=protein kinase C. PLCβ=phospholipase C β. ROS=reactive oxygen species. TCR=T cell receptor. UPR=unfolded protein response. *Dose-dependent. Reproduced from Peter et al.[2]