Personalized Medicine for HLA-associated Drug-hypersensitivity Reactions

Mandvi Bharadwaj; Patricia Illing; Lyudmila Kostenko


Personalized Medicine. 2010;7(5):495-516. 

In This Article

Delayed Hypersensitivity to Aminopenicillins

Although β-lactam penicillins frequently induce IgE-mediated ADR, DTH reactions are also observed. In vitro studies have shown that T cells of the CD4+ phenotype can be proliferated from the blood of hypersensitive individuals and that stimulation of these cells is dependent on HLA-DR.[92] Furthermore, such T cells have been stimulated by synthetic peptides covalently modified with penicillin G in the context of HLA-DRB1, demonstrating that penicillin haptenated self peptides may be the antigens causing these hypersensitivities.[93,94] By contrast, cells isolated from skin infiltrate tend to be of the CD8+ phenotype, and show cytotoxicity towards autologous keratinocytes and β cells.[95] Delayed hypersensitivity to aminopenicillins, often involving MPE, have been associated with HLA-A2 and HLA-DRw52, present in 50 and 83.3% of patients, and 12.8 and 35% of controls, respectively.[96] However, this association has not been seen in other studies and in vitro studies have shown the presentation of penicilloyl peptides by other HLA types.[93] The apparent involvement of both class I and class II alleles in these hypersensitivities may be owing to differing hypersensitivity phenotypes, or indicate an interplay of both CD4+ and CD8+ T cells in these hypersensitivities, already made complex by the involvement of other immune contributors such as IgE.[92]