Drug-antibody complex

Type 3, immune complex vasculitis (serum sickness, Arthus reaction). Drug-antibody complexes precipitate on vascular walls, complement is activated, and an inflammatory reaction is triggered. Attracted neutrophils, in a futile attempt to phagocytose the complexes, liberate lysosomal enzymes that damage the vascular walls (inflammation, vasculitis). Symptoms may include fever, exanthema swelling of lymph nodes, arthritis, nephritis, and neuropathy. 

Double Antibody Technique. Although the drug-antibody complex is large it is still soluble. It can be converted into an insoluble form, which can be centrifuged, by the addition of a second antibody (the precipitating antibody) raised against the globulins of the animal in which the first antibody was raised. The free fraction is then simply decanted out of the tube. 

The principal components in radioimmunoassay (RIA) are a drug labelled with a suitable radioisotope, an antibody specific to that drug, and the assay sample. The drug-antibody complex (bound drug) must be separated from the free drug in the later stages of the assay. 

Thrombocjhopenia is often reported with quinine. It is probably due to hjrpersusceptibility rather than a toxic effect, since even the ingestion of minimal amounts of quinine, such as those present in commercial tonic waters, can cause it. A drug-antibody complex has been... 

Shulman (1963), also working with quinidine, proposed an alternative explanation to explain the mechanism. He relegates the platelets to a passive role and considers them to be specialized cells capable of adsorbing onto their surface a drug-antibody complex. This hypothesis was a deduction based on the study of a steric and kinetic model for the immunoreactants involved in platelet lysis (Shulman 1958). By varying the concentrations of the reactants in the model, Shulman was able to show that there was only stoichiometric combination between the four reactants, antibody, antigen, platelets, and complement, and that the interactions were most likely bimolecular and sequential. The most probable sequence appeared to be first an initial combination of quinidine with either antibody of platelets, followed by the formation of the complete antibody-quinidine-platelet... 

Support for Shulman s hypothesis would be the in vitro demonstration of platelet damage by drug-antibody complexes or the demonstration of such complexes in the sera of patients with thrombocytopenia. Despite numerous attempts by various investigators (Cronin 1965 Amos 1967, unpublished work) no evidence of this type could be found. 

Stibophen is not a cardiovascular drug, but the proposed mechanism by which stibophen induces anemia would also fit the data generated by Freedman et al. (1956) for quinidine anemia and be compatible with Shulman s passive bystander hypothesis for drug-induced thrombocytopenia (Shulman 1958). The essential feature of the mechanism is the formation of a drug-antibody complex which passively adheres to red cells. Complement is fixed by the complex and the cells are lysed as a result. 

Whereas initially the focus on antibody-based therapies was on cancer, anti-TNFa antibodies in particular have recently proven powerful in the therapy of chronic inflammatory diseases such as inflammatory bowel disease and rhemnatoid arthritis [71], These antibodies complex serum TNFa, the clinical benefit to RA patients most likely being the reduction of pro-inflammatory IL-6 and acute phase protein levels [9], Although they are directed against soluble proteins and as such will not serve as a drug carrier, they do show that targeted, i.e. selective, interference with a specific molecule or process can have a powerful effect without significant concomitant toxicity. 

IVpe 2, cytotoxic reaction. Drug-antibody (IgG) complexes adhere to the surface of blood cells, where either circulating drug molecules or complexes al-Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of iicense. 

Fig. 6.4 A four-parameter logistic standard curve depicting a competitive assay. In this format the antibody (Ab) is present in a limited amount. The known amount of labeled drug competes with the drug analyte in the sample for the limited sites of the Ab. The response factor produced by the label antigen-antibody complex (Ag-Ab) is inversely proportional to the concentration of the drug analyte in the sample. In this example the % B/B0 (% label bound at concentration X divided by...

The potential for immune responses against biologies (hypersensitivity, anti-drug antibodies, immune complexes, etc.) is something that most stent (alone or as drug-coated stents) manufacturers have not had to consider in prior development programs. 

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