The lymphocyte transformation test for diagnosis of drug-induced occupational allergy

Twenty-five workers with clinically diagnosed or suspected occupational hypersensitivity caused by contact with bacampicillin, alprenolol, and/or quinidine were studied by the lymphocyte transformation test and by skin tests. Ten healthy exposed workers, 16 job applicants, and seven healthy nonexposed laboratory workers served as control subjects. Lymphocyte transformation was measured by 3H-thymidine uptake into DNA and by counting of lymphoblasts on cell smears. Lymphocytes from workers with contact eczema or with eczema in combination with conjunctivitis and rhinitis responded to offending drugs in vitro as demonstrated by an increased 3H-thymidine incorporation and by the presence of lymphoblasts in the cultures. In vitro proliferative responses were reproduced during a 4-year period. Drug-specific allergy was confirmed by positive patch test in most workers with eczema. In addition, bacampicillin-specific lymphocyte proliferation was also observed in workers with suspected bacampicillin hypersensitivity but with negative skin tests. They suffered mostly from eczema in combination with conjunctivitis and rhinitis or from conjunctivitis/rhinitis only. Lymphocytes from most control subjects did not respond in vitro to bacampicillin, alprenolol, or quinidine. Weak proliferative responses to bacampicillin were observed in two of the 16 job applicants. The exquisite specificity of drug-induced lymphocyte responses is demonstrated. Thus, lymphocytes from a quinidine-sensitive worker did not respond in vitro to the quinidine stereoisomer, quinine. Furthermore, lymphocytes from a bacampicillin-sensitive worker responded to some penicillins, such as pivampicillin and ampicillin, but not to others, such as benzylpenicillin or pivmecillinam. These data suggest the role of N-acylamido side chain in the sensitization of lymphocytes from this particular donor. In conclusion, lymphocyte transformation test can be used for the detection of offending agents in occupationally sensitized workers. Furthermore, lymphocytes from such individuals may serve as a model for study of specificity of cellular reactions underlying drug-induced hypersensitivity.