Measurement of lymphocyte activation by a chromatin topooptical reaction. II. Application for detecting drug allergy. A clinical and experimental study.

Lymphocyte chromatin activation was measured in 18 clinical cases of suspected or proven drug allergy as well as in 4 other persons with neither history nor signs of hypersensitivity. The different drugs were tested in the reaction in such dilution that the final concentrations ranged between 50 and 10.000 nanomoles. Within this range between 100 and 1250 nanomoles a bellshaped dose response curve was found in all drug-allergic subjects, measuring the neutral-red chromatin topooptical reaction. At the peak of this curve signs of cytotoxicity could be demonstrated with appreciable chromatin "desactivation", an increase of protein-like substance in the cells' supernatant and a morphological cellular damage. The exact drug concentration at which the lymphocyte autocytotoxicity occurred was inversely proportional with the extent of drug allergy in a given patient. The average lymphocyte chromatin birefringence measured at different non-cytotoxic drug concentrations was directly proportional with the extent of drug allergy. The ratio of the above characteristics gave a score (with the dimension of cm2/microM) which corresponded to the clinical picture. The score was low (55,7 +/- 5,8 cm2/microM) in the control subjects as well as in the drug allergic ones tested with other, i.e. nonsensitizing drugs. The score was high, (309,8 +/- 54,4 cm2/microM) however, when drug allergic patients' lymphocytes were challenged by the proper drug(s). There was neither false negativity in the positive group nor false positivity in the negative group of patients. Scores above 75 cm2/microM are considered as positive, those above 80 cm2/microM are undoubtedly positive. The relation of this rapid test to the lymphocyte transformation test as well as its advantages over the latter are discussed.