Cutaneous Anaphylactic Reactions with Antibodies of Different Qualities.

Publisher Website
Google Scholar
Abstract
Conclusions These results indicate that a 7S γ2 rabbit antibody having a low affinity for its antigen was equally as efficient as a 7S γ2 high affinity antibody in producing cutaneous anaphylaxis in guinea pigs when abundant antigen was present. However, when the concentration of antigen in the reaction was reduced the antibody of low affinity was not as potent as the antibody of higher affinity. A possible explanation of the inefficiency, marked by a slow rate of development and at times less severe anaphylactic reaction, was found to lie in a relatively slower rate of association noted between the absorbed antiserum and its antigen (Fig. 1). This slower rate of association may well bear causal significance when considering the finding that when one merely increases the concentration of antigen in the circulation, the rate of anaphylactic response of the slowly associating antiserum was increased to equal that of the control, rapidly associating antiserum (Table I). These latter conditions favored more rapid and complete binding of the lower affinity antiserum by antigen. These findings fail to support the possibility that the absorbed, slower associating antibody was less capable of “fixing” to tissues or for other reasons less capable of reacting, since merely by raising the dosage of antigen it became fully reactive in vivo. Other tests failed to show significant differences between antibodies in the 2 antisera: both were 7S, γ2 globulins as determined by density gradient ultracentrifugation and radioimmunoelectro-phoresis. When mixed with antigen they both fixed abundant hemolytic complement. The antigen-antibody dissociation rates of the 2 antisera were not appreciably different considering the amount of time required to demonstrate as much as 15-20% difference. Further, in other unpublished studies in this laboratory, results similar to those herein reported have been found using anti BSA obtained from individual rabbits after primary immunization and absorbed once with a small amount of antigen. This diminishes the possibility that the results could be explained by some unique quality of the absorbed antiserum. The role played by low affinity antibody in immunopathologic lesions may be considerable. In serum sickness the antibody responsible is without much doubt of relatively low affinity. In this disease alone such diverse lesions as endothelial proliferation, increased glomerular permeability, vascular necrosis and anaphylactic alterations in vessels take place. Anaphylactic reactions bringing about an increase in vascular permeability may be of special importance in causing circulating antigen-antibody complexes to localize in vessel walls to produce the lesions. Anaphylaxis may thus act as a trigger mechanism in initiating the development of the disease (11-13). The extent to which low affinity antibody may influence the development of related lesions has not been determined. These studies, along with those of Osler(l), indicate that low affinity antibody may be less efficient in precipitating anaphylactic responses under conditions of low concentrations of antigen. However, when an optimum of antigen is present such antibody is fully reactive.