Table 3.
Risk components identified in development of EN
| Component/process within pathogenesis | Risk components/pathways | Reference | |
|---|---|---|---|
| HLA‐TCR interaction | HLA class I | Various HLA class I risk alleles | 27, 80, 81 |
| TCR clonotype: presence of a TCR able to interact with drug/HLA complex | Random TCR recombination | 119, 120 | |
| Immunologic history | |||
| Thymic TCR selection influenced by proteasomal activity | |||
| Availability of drug/drug metabolite | Metabolic genes: e.g. CYP2B6 and GSTM1 (nevirapine), CYP2C9 (phenytoin) | 124, 125, 126 | |
| Drug transporters, e.g. ABC transport pathway | 120, 130 | ||
| Peptide sequence and quantity | Peptide generation: e.g. ERAP2, proteasomal function | 120, 122, 123 | |
| Immune response | Lymphocyte proliferation | Apoptosis | 120 |
| Proteasomal pathway | 120, 137 | ||
| Lymphocyte activation | Co‐inhibitory pathways PD‐1 or CTLA4 | 135 | |
| CD4 + T cells | Th17‐cells producing IL‐17 | 136 | |
| Regulation of cytokine production | Proteasomal pathway | 121 | |
| Act1 signalling | 133 | ||
| Innate immune response | TLR3, IL4R, IL‐13, PTGER3 | 138, 139 | |
| Other | PSORS1C1, HCP5 | 95, 132, 134 |