Immunogenicity allergic reaction

The long-term toxicities of concern are opportunistic infections, lymphoproli-ferative disorders, and immunogenicity, manifesting as tachyphylaxis and/or allergic reactions. Preclinical approaches which serve to identify these as potential hazards to humans of a biologic drug moiety are thus needed. 

A variety of assays have been designed and validated to measure specific antibodies in the sera of treated animals. In addition efforts have been paid to minimizing the immunogenicity of therapeutic proteins. As these issues are addressed comprehensively in another chapter of this volume, the focus here will be on predicting problems that may ensue from the presence of such antibodies, namely hypersensitivity reactions. Presumably because allergic reactions have long been considered to be nonreproducible in animal models, limited efforts have been paid to designing predictive animal models until recently. Unexpectedly, the consequence is that no adequately standardized and validated model is available at the present time. 

Allergy to icodextrin was the most likely explanation for the severe cutaneous reaction. The epitope(s) for allergic reactions to dextrans have not been defined, although they are undoubtedly immunogenic. It is possible that the same or a similar epitope may be responsible for allergic reactions to icodextrin. 

It is proposed therefore that while the stimulation of cytokine production per se is a reflection of the inherent immunogenicity of a chemical, the selectivity of cytokine secretion is a function of the quality of immune response provoked and, as a consequence, is indicative of the type of allergic reaction that will develop subsequently. If such is the case then it should be possible to classify chemical allergens on the basis of cytokine selectivity. Such cytokine fingerprinting is particularly attractive as it would permit, in a single integrated... 

Immunogenicity is undesirable because it can be the source of a number of safety concerns, such as hypersensitivity and allergic reactions, thrombocytopenia, anemia, etc. Very problematic with recombinant therapeutic proteins, but fortunately extremely unlikely with antibodies, are... 

In summary, it seems firmly established that penicillin polymers, and especially polymers formed from aminopenicillins, exhibit a strong penicilloyl-specific antigenicity and it is likely that they may play a part in the elicitation of some clinical allergic reactions to penicillin preparations. The question of immunogenicity of penicillin polymers is still to be fully resolved. 

In man, allergic reactions have been in reported in patients with no prior history of penicillin allergy, leading to the assumption that cephalosporins may be immunogenic by themselves (Kaplan and Weinstein 1967 Abraham et al. 1968 a, b Molthan 1969 Saleh and Tischler 1974). 

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