The diagnostic value of intradermal tests with penicilloyl-dextran and aspiryl-polylysine.

Intradermal tests (i.d.t.

On the relation between the formation of antihapten and anti-carrier protein antibodies in the immune response induced by conjugates of various haptens with homologous serum proteins.

Rabbits inoculated with conjugates of homologous serum with ortho-aminophenol (OAP), para-aminophenol (PAP), 3-hydroxy-sulfanilamide (3-HS), DOPA and alpha-methyldopa (alpha MD), 5-aminosalicylic acid (5-ASA) and 3-hydroxy-para-aminobenzoic acid (3-HPABA) give rise to both hapten specific and anti-carrier protein antibodies. By contrast, the conjugates of homologous serum with penicilloyl (P) hapten induced only antihapten antibodies. The conclusion is, therefore, drawn that the formation of anti-carrier antibodies upon inoculation with conjugates of various haptens appears to be dependent on the nature of hapten in the conjugate.

Haptenic properties of drug metabolites with ortho- or para-aminophenolic structure.

3-Hydroxy-sulfanilamide (3-HS), a biotransformation product of sulfanilamide, 3-hydroxy-para-aminobenzoic acid (3- HPABA ), a biotransformation product of procaine and para-aminobenzoic acid, as well as 5-aminosalicylic acid (5-ASA), a bacterial split product of salicylazosulfapyridine (Sulfasalazine, Salazopyrin ) in the gut, were shown to react spontaneously with and to bind covalently to proteins by simple incubation at alkaline pH. When administered incorporated in incomplete Freund adjuvant into rabbits, the conjugates of these haptens with normal rabbit serum proteins (NRS) give rise to both hapten specific and anti-NRS antibodies. The haptenic properties of these drug metabolites are apparently due to the presence in their molecules of an ortho- or para- aminophenolic structure that renders them capable to generate spontaneously highly reactive quinoneimines .

Spontaneous formation of immunogenic conjugates by 3-hydroxy-para-aminobenzoic acid--a biotransformation product of procaine and para-aminobenzoic acid.

3-Hydroxy-para-aminobenzoic acid (3-HPABA), a biotransformation product of procaine and para-aminobenzoic acid, is capable of binding covalently to proteins by simple incubation at alkaline pH. When administered incorporated in Freund adjuvant to rabbits, 3-HPABA conjugates with normal rabbit serum proteins (3-HPABA-NRS) give rise to both hapten specific antibodies and anti-NRS antibodies. Cross immunological reactions were found between 3-HPABA and ortho-aminophenol (OAP) and 3-hydroxy-sulfanilamide (3-HS) immunological systems, but not between 3-HPABA and para-aminophenol (PAP) and 5-aminosalicyclic acid (5-ASA) immunological systems.

Spontaneous formation of immunogenic conjugates by 5-aminosalicylic acid--a biotransformation product of salicylazosulfapyridine.

5-Aminosalicylic acid (5-ASA) reacts readily with proteins at alkaline pH and forms conjugates capable to induce hapten specific antibodies in rabbits. Extensive immunological cross reactions have been found between 5-ASA and para-aminophenol (PAP) immunological systems, but no cross reactions were found between 5-ASA and orto-aminophenol (OAP) immunological systems. Moderate cross reactions were found, occasionally between 5-ASA, 3-hydroxy-sulfanilamide (3-HS) and alpha-methyldopa (alpha MD) immunological systems.