Immunogen definition

The definition of risk is the probability times the consequences (Figure 20.1). So the probability of an immune response is not synonymous with its risk. A high risk can be associated with a relative high probability, but also with a low probability if the consequences are severe. For example, the probability of an immune response to epoetin is rather low, but one of the consequences, antibody-induced severe anemia, is severe [3], This makes the risk of immunogenicity of epoetins relatively high. 

Both pork and human insulin are definitively less immunogenic than beef insulin, producing fewer circulating insulin antibodies, but several studies have indicated no detectable change in antibody concentrations on switching from pork to human insulin or vice versa. Antibodies cause lipoatrophy and are responsible for the substantial insulin resistance seen in some patients, but both events are rare now that purified pork insulin is in common use. Interest has recently been revived in the possible contribution of antibodies in modifying metabolic control. In the short term and under hospital conditions, they are known to prolong the intravenous half-life of injected insulin and to delay the appearance in the circulation of a subcutaneously administered bolus dose. 

This chapter deals with the assessment of definitive and relative quantitative assays. A good reference on the analytical validation of a quasi-quantitative assay is a white paper on immunogenicity by Mire-Sluis et al. [6] and the guidance on assay development and validation for high-throughput screening developed by scientists from NIH and Eli Lilly Company [7]. 

In one clinical situation, the nature of the autologous carrier may be rather clearly defined this is in drug-induced hemolytic anemia based on immunologic mechanisms. It has been shown that destruction of erythrocytes is due to interaction of IgG antibodies with the red cell membrane after its appreciable penicilloy-lation during therapy with high doeses of penicillin (Levine and Redmond 1967). The antibodies involved were penicilloyl specific but it appeared possible that modified structures of the red cell surface are also contributing to the specificity. If this can be substantiated, the erythrocyte will be definitively implicated as the actual immunogenic carrier. 

The immunogenicity of penicilloic acids as such has not yet been definitely established. On the one hand, the fact that a selected number of penicillin-sensitive patients very strongly react to benzylpenicilloic acid, sometimes to the exclusion of other determinants (Levine and ] dmond 1969 Gattlen and Peter 1976 ... 

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