Abstract
Human application of monoclonal antibodies (mAbs), enzymes, as well as contrast media and many other particulate drugs and agents referred to as “nanomedicines”, can initiate pseudoallergic hypersensitivity reactions, also known as infusion reactions. These may in part be mediated by the activation of the complement system, a major humoral defense system of innate immunity. In this review, we provide a brief outline of complement activation-related pseudoallergy (CARPA) in general, and then focus on the reactions caused by mAb therapy. Because the alternative pathway of complement activation may amplify such adverse reactions, we highlight the potential use of complement factor H as an inhibitor of CARPA.
Highlights
Monoclonal Antibodies and Hypersensitivity ReactionsMonoclonal antibodies are made by identical immune cells that are all clones of a unique parent B cell, and are widely used both in basic research and the therapy of various diseases
The artificial inhibitor, recombinant mini-factor H [33], which unites the N-terminal complement-regulatory domains and the C-terminal host surface recognition domains of the natural molecule, was even more effective in inhibiting such complement activation compared with factor H [30]. These data suggest that factor H-based complement inhibition could be a viable strategy to prevent or mitigate complement activation-related pseudoallergy (CARPA) induced by nanomedicines, including therapeutic monoclonal antibodies (mAbs)
The prevention of infusion reactions (IRs) induced by mAbs can be addressed the same way as the prevention of similar adverse reactions occurring upon nanomedicine treatments
Summary
Monoclonal antibodies (mAbs) are made by identical immune cells that are all clones of a unique parent B cell, and are widely used both in basic research and the therapy of various diseases For the latter purpose, one of the main goals of scientists became to create “fully” human products to reduce the side effects of humanized or chimeric therapeutic antibodies. It has increasingly been recognized that a substantial portion of acute allergic reactions, whose symptoms fit in Coombs and Gell’s Type I category, are not initiated or mediated by pre-existing IgE antibodies. These reactions are known to be “pseudoallergic”.
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