The prevalence of β-lactam hypersensitivity in patients with cystic fibrosis makes it increasingly difficult to treat infective exacerbations effectively because of the restriction in available antibiotics. El-Ghaiesh et al. used cloned T-cells expressing a single T-cell receptor from five piperacillin-hypersensitive patients to characterize both the cellular pathophysiology of the reaction and antigen specificity to define the mechanism of activation of T-cells by piperacillin. Stimulation of CD4+ and CD8+ clones with piperacillin was found to be highly specific in terms of drug structure and dependent upon the formation of protein adducts. Piperacillin-modified albumin was the only conjugate detected in cell culture systems; adduct formation was concentration- and time-dependent, and protein processing was a prerequisite for the activation of T-cells. Pretreatment of albumin with flucloxacillin blocked piperacillin-albumin binding and the piperacillin-specific T-cell response. These data describe the cellular processes that underlie the structural specificity of piperacillin antigen binding and suggest that there may be some merit in studying the clinical relevance of administering combinations of β-lactam antibiotic in patient groups where a high prevalence of hypersensitivity reactions is seen.
See article at J Pharmacol Exp Ther 2012, 341:597–610.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics