Specificity of Rabbit Antibody to Formaldehyde Treated Rabbit Serum Albumin

Formaldehyde is a common cause of allergic contact dermatitis in man, but unlike many sensitizing agents, it is probably too small to be a hapten. Formaldehyde reacts with the primary amino, groups of proteins to form methylol groups or methylene bridges. Similar chemical substitutions are known to create new antigenic determinants in proteins by changing the net charge and native conformation. This study was designed to explore the mechanism of formaldehyde hypersensitivity. Native rabbit serum albumin altered by reactivity with formaldehyde-C14 was immunogenic in the rabbit. Antisera reacted with a specific fraction of the immunizing antigen obtained by cationic exchange chromatography. The moles of formaldehyde taken up by this fraction were less than the number of primary amino groups blocked, indicating that methylene bridges were formed within or between molecules. The antiserum to formaldehyde-altered RSA did not precipitate with native RSA, acetylated RSA or other formaldehyde-altered proteins. Antisera prepared to acetylated RSA did not react with formaldehyde-altered RSA. These data suggest that these antibodies are primarily directed toward a new conformation of albumin produced by methylene bridges