Using the ELISA and passive haemagglutination test we investigated the humoral immune response induced by long-term administration of benzylpenicillin in patients. After the second week of the course in twenty-four out of sixty-one patients, synthesis of benzylpenicilloyl (BPO) specific IgG, IgA, IgM and/or IgE could be demonstrated. BPO-specific IgE was always found in combination with BPO-specific IgG and/or IgM. No difference in the humoral immune response was found between patients who developed clinical hypersensitivity reactions and those who did not.
In a follow-up study the disappearance of BPO-specific immunoglobulins of all classes was observed. Results of the epicutaneous tests showed that a long-term course of benzylpenicillin did not evoke delayed hypersensitivity. However intracutaneous tests with benzylpenicilloyl-polylysine or benzylpenicillin showed positive immediate type reactions. From the results it can be concluded that a BPO-specific IgE response is not necessarily associated with the development of a clinical hypersensitivity reaction.