Studies on the Immune Response to Penicillin and Cephalothin in Humans

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Abstract
The characteristics of immunohematologic reactions to cephalothin were investigated with emphasis on the incidence and mechanism of development of positive antiglobulin tests. Three hundred twenty direct antiglobulin tests were performed on 97 patients who received cephalothin at an average dose of 6.3 g/day and for an average of 5.5 days. Four of the 97 patients developed a positive antiglobulin test for an incidence of 4%. Studies were done concerning the mechanism of the positive direct antiglobulin tests. The data indicate that nonimmunologic binding of proteins occurs in vitro since multiple absorptions of a serum with cephalothin-sensitized erythrocytes revealed that the cephalothin-sensitized cells absorb IgG and other serum proteins, even after repeated absorptions sufficient to remove all cephalothin antibodies. Non-immunologic binding of proteins to cephalothin-sensitized red cells was further confirmed by demonstrating the absorption of complement (C3) from EDTA-plasma, and by the absorption of albumin. Such a mechanism may operate in vivo since cephalothin, when added to whole blood at a concentration of 500 µg/ml, causes protein absorption to the erythrocytes. An immune mechanism causes positive antiglobulin tests in vivo as evidenced by the fact that eluates from patients' erythrocytes react with cephalothin-and penicillin-sensitized erythrocytes but not with non-sensitized erythrocytes. Further, eluates from Rh sensitized erythrocytes did not react with cephalothin-sensitized red cells indicating that the concentration of antibody protein in such eluates is not high enough to produce positive indirect antiglobulin tests by the mechanism of non-immunologic absorption of proteins. Studies characterizing the serum cephalothin antibodies revealed IgM antibodies in 88% of 40 sera tested. Although IgG antibodies occurred in only 25% of these sera, the sera of four patients having a positive antiglobulin test all contained high titer IgG antibodies. Absorption of sera of patients with positive antiglobulin tests with penicillin-sensitized erythrocytes revealed varying degrees of cross-reactivity with such erythrocytes.

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