This article offers fundamental information on CARPA: a brief history, nomenclature issues, incidence, classification of reactogenic drugs and symptoms, and the mechanisms of C activation through different pathways.
Intravenous injection of a variety of nanotechnology-enhanced (liposomal, micellar, polymer-conjugated) and protein-based (antibodies, enzymes) drugs can lead to hypersensitivity reactions (HSRs), also known as infusion or anaphylactoid reactions.
The molecular mechanism of mild to severe allergy symptoms is unknown; however, in many cases, a significant cause or contributing factor is the activation of the complement (C) system.
The clinical relevance of C activation-related HSRs, a non-IgE-mediated pseudoallergy (CARPA), lies in their unpredictability and potential for a lethal outcome. Accordingly, there is an unmet medical need to develop laboratory assays and animal models that quantify CARPA.
It is noted that anaphylatoxin-induced mast cell release may not entirely account for the severe reactions; a "second hit" on allergy-mediating cells may also contribute.
In addressing the increasing requirements for CARPA testing, the review evaluates the available assays and animal models. It proposes a possible algorithm for the screening of reactogenic drugs and hypersensitive patients.
Finally, an analogy is proposed between CARPA and the classic stress reaction, suggesting that CARPA represents a "blood stress" reaction, a systemic fight of the body against harmful biological and chemical agents via the anaphylatoxin/mast-cell/circulatory system axis, in analogy to the body's fight of physical and emotional stress via the hypothalamo/pituitary/adrenal axis.
In both cases, the response to a broad variety of noxious effects is funneled into a uniform pattern of physiological changes.
