Non-Specific Precipitation of Sulfathiazole Azo-Conjugates by Immune Sera;Inhibition and Complement-Fixation

Abstract

A case of acquired sulfathiazole sensitivity exhibiting a specific response to administration of single doses of sulfathiazole has recently been described. 1 Similar observations have been made on a patient sensitized to sodium sulfapyridine. 2 The specificity of the response prompted a search for the presence of antibodies specific for the sulfonamide grouping. Attempts to detect such antibodies to pure sulfonamide drug antigens have failed; 3 test antigens were therefore prepared by coupling diazotized sulfathiazole with crystalline horse serum albumin, horse serum globulin, and human serum globulin. 4 Similar azo antigens have already been employed in studies of human sulfonamide sensitivity with negative results 5 6 although the development of specific antibodies by the rabbit immunized with sulfonamide azo proteins has been described. 3 7

The sulfathiazole azo proteins precipitated with some supposedly normal and several unrelated immune sera. Similar precipitation of azo proteins, in high concentration, was encountered by Land-steiner and Van der Scheer, 8 who diluted their antigens to eliminate the non-specific precipitation. Resorcinol-disazosulfathiazole (ResDST) was also synthesized 9 to determine whether exclusion of protein from the molecule would eliminate non-specific precipitation. The unrelated sera,∗ however, also precipitated with ResDST. The amount of precipitation depended upon the proportion in which serum and ResDST were mixed and inhibition zones were encountered with excess of antibody or antigen (Table I). With certain serum-dye ratios exposure to 37°C resulted in solution of the precipitate, the amount of precipitate in other mixtures changing in character from dispersed floccules to a cohesive disc. Precipitations of other azo proteins and horse antipneumococcal sera have already been described; 10 11 12 rabbit antipneumococcal sera, however, failed to precipitate. 11

It seemed of interest to determine whether the homologous pure sulfonamide drugs or their neutral azo components would inhibit the precipitation between sulfathiazole azo protein and the non-azo-specific antipneumococcal rabbit serum.