The role of enzymatic coupling of drugs to proteins in induction of drug specific antibodies.

Isoniazid and hydralazine were covalently crosslinked by epidermal transglutaminase to serum and cell nuclear proteins. Albumin and nucleohistones were excellent acceptors of these drugs in serum and nuclear extracts, respectively. Drug-albumin and drug-histone conjugates were highly antigenic in rabbits within 4 weeks, eliciting drug-specific antibodies in all immunized animals. A radioimmunoassay for antibodies to isoniazid were developed, using a standard drug-albumin conjugate. The methods described here of enzymatic crosslinking of drugs to proteins facilitate studies of drug-induced hypersensitivity in animals and man.