Hypersensitivity Reactions to Biologicals: True Allergy?

Abstract

Biological agents are a growing class of drugs that have modified the treatment of multiple chronic immune-mediated and tumor diseases. Despite these positive aspects, some issues may exist during the treatment with biologicals such as an increased risk of infections as well as the occurrence of infusion reactions, which in some cases could be severe and life-threatening. Concerning infusion reactions, it is important that allergists recognize the symptoms and know their underling pathogenic mechanisms in order to perform a correct diagnosis. The safety profile of biologicals is negatively impacted by their immunogenicity, which leads to the production of specific anti-drug antibodies. Various types of anti-drug antibodies have been demonstrated, including the IgE isotype, classically responsible for type I hypersensitivity reactions. However, non-IgE anti-drug antibodies, mostly represented by IgG, may lead to infusion reactions through complement activation or, as clearly shown in animal models, involving FcγRIII, basophils, and macrophages. Of note, a proportion of infusion reactions are not antibody-mediated such as the so-called cytokine-releasing syndrome, which may be clinically indistinguishable from the classic antibody-mediated hypersensitivity reactions. Knowledge of pathophysiology of infusion reactions may enable a correct diagnostic work-up to be set up in reactive patients. In fact, both in vitro and in vivo tests are available for detecting anti-drug antibodies towards biologicals, although they have not yet been fully standardized. Taking into account the above concerns, for these diagnostic procedures, particularly in vivo testing, physicians should be equipped with specific allergological expertise, to overcome possible issues in this new and specific of clinical field.