Long-lasting reactivity and high frequency of drug-specific T cells after severe systemic drug hypersensitivity reactions.
BACKGROUND
Drug-reactive T cells are involved in most drug-induced hypersensitivity reactions. The frequency of such cells in peripheral blood of patients with drug allergy after remission is unclear.


OBJECTIVE
We determined the frequency of drug-reactive T cells in the peripheral blood of patients 4 months to 12 years after severe delayed-type drug hypersensitivity reactions, and whether the frequency of these cell differs from the frequency of tetanus toxoid-reactive T cells.


METHODS
We analyzed 5 patients with delayed-type drug hypersensitivity reactions, applying 2 methods: quantification of cytokine-secreting T cells by enzyme-linked immunospot (ELISpot), and fluorescent dye 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity distribution analysis of drug-reactive T cells.


RESULTS
Frequencies found were between 0.02% and 0.4% of CD4(+) T cells reacting to the respective drugs measured by CFSE analysis, and between 0.01% and 0.08% of T cells as determined by ELISpot. Reactivity was seen neither to drugs to which the patients were not sensitized nor in healthy individuals after stimulation with any of the drugs used.


CONCLUSIONS
About 1:250 to 1:10,000 of T cells of patients with drug allergy are reactive to the relevant drugs. This frequency of drug-reactive T cells is higher than the frequency of T cells able to recognize recall antigens like tetanus toxoid in the same subjects. A substantial frequency could be observed as long as 12 years later in 1 patient even after strict drug avoidance. Patients with severe delayed drug hypersensitivity reactions are therefore potentially prone to react again to the incriminated drug even years after strict drug avoidance.
Beeler
Andreas
A
Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, Bern, Switzerland.
Engler
Olivier
O
Gerber
Basil O
BO
Pichler
Werner J
WJ
D000328:Adult; D000900:Anti-Bacterial Agents / Q000276:immunology*; D000927:Anticonvulsants / Q000009:adverse effects / Q000276:immunology*; D002220:Carbamazepine / Q000009:adverse effects / Q000276:immunology; D004342:Drug Hypersensitivity / Q000209:etiology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects / Q000276:immunology; D013388:Succinimides; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D013745:Tetanus Toxoid / Q000276:immunology
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D005452:Fluoresceins; D005456:Fluorescent Dyes; D013388:Succinimides; D013745:Tetanus Toxoid; D002220:Carbamazepine; D010672:Phenytoin