Hook effect
The hook effect refers to the prozone phenomenon, also known as antibody excess or the Postzone phenomenon, also known as antigen excess. It is an immunologic phenomenon whereby the effectiveness of antibodies to form immune complexes can be impaired when concentrations of an antibody or an antigen are very high. The formation of immune complexes stops increasing with greater concentrations and then decreases at extremely high concentrations, producing a hook shape on a graph of measurements. An important practical relevance of the phenomenon is as a type of interference that plagues certain immunoassays and nephelometric assays, resulting in false negatives or inaccurately low results. Other common forms of interference include antibody interference, cross-reactivity and signal interference. The phenomenon is caused by very high concentrations of a particular analyte or antibody and is most prevalent in one-step (sandwich) immunoassays.[2][3]
In vivo observations[edit]
Lewis Thomas described in his memoir a physiologic experiment of 1941 in which he observed the prozone effect in vivo: immunity in rabbits to meningococcus, which was robust, unexpectedly decreased when immunization was used to induce a heightened antibody response.[10] In other words, getting the rabbits' bodies to produce more antibodies against this bacterium had the counterproductive effect of decreasing their immunity to it. From the viewpoint of an overly simplistic notion of the antibody/antigen relationship, this seems paradoxical, although it is clearly logical from a viewpoint duly informed by present-day molecular biology. Thomas was interested in pursuing this physiologic research further, and remained so for decades afterward, but his career took him in other directions and he was not aware of anyone having pursued it by the time of his memoir.[10] One kind of relevance that he hypothesized for this in vivo blocking antibody concept was as a driver of human susceptibility to certain infectious diseases.[10] In the decades since, the concept has also been found to have clinical relevance in allergen immunotherapy, where blocking antibodies can interfere with other antibodies involved in hypersensitivity and thus improve allergy treatment.[11]