Drug-specific antibodies in patients receiving captopril

IgG anti-captopril (CP) antibody activity was detected by enzyme-linked immunosorbent assay (ELISA) in serum from two out of 45 patients receiving the drug (25-75 mg day-1). Five of the 45 patients, including one whose serum was antibody-positive, suffered skin rashes which were thought to be drug-induced. The specificity of the antibody for the disulphide-conjugated form of captopril was established as follows: serum IgG bound to disulphide-linked captopril-human albumin (CP-S-S-HSA) conjugate but not to HSA; binding of IgG to CP-S-S-HSA was inhibited by disulphide-linked captopril-ovalbumin (CP-S-S-OVA) conjugate and captopril disulphide (CP-S-S-CP). The structurally related drug D-penicillamine (PA) in disulphide-linked form (PA-S-S-OVA and PA-S-S-PA) was without inhibitory activity. The inhibitory preparations of CP-S-S-OVA and CP-S-S-CP were shown to be inactive in an ELISA for human IgG directed against the unrelated benzylpenicilloyl antigen. Since disulphide-linked CP-plasma protein conjugates are formed extensively in vivo, and since the antibodies we describe are directed against CP in disulphide-linked form, it appears that CP may be immunogenic in some patients receiving the drug.