Summary
Objective. To analyze the significance of the formation of non-covalent drug-protein bonds for drug hypersensitization reactions based on the latest literature data. Understanding the mechanism of drug hypersensitization would al low to im prove diagnostics, personalize treatment.
Literature review. Drug hyper sensitivity reactions (DHR) are heterogeneous and a typical immune responses induced by drugs. For a long time the interpretation of DHR mech a nisms has been based on hapten theory but there is growing evidence that the for ma tion of non-covalent drug-protein bonds is of much greater importance. The main non-covalent interactions are mimicry (false antigen), increased anti body affinity and pharmaco logical stimulation of immune receptors (p-i concept). Fake antigen is a non-covalently linked drug-pro tein complex which mimics covalent complex and is capable of binding to IgE on mast cells. Small amounts of these non-co va lent drug- protein complexes cause desensitization of mast cells, large amounts of degranulation and anaphylactic re ac tion. Some drugs may non-covalently bind to circulating antibodies and increase their affinity for tar get cells thereby in ducing immune responses such as thrombocytopenia, hemolyticanemia. The concept of p-i is based on the fact that drugs can bind to immune receptors (TCR and HLA) through non-covalent bonds. Modi fied immune receptors in duce allostimulation and T-lymphocytes activation and proliferation. The main clinical out comes of the p-i re sponse are maculopapular exanthema (MPE), Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), drug response to eosinophilia and sys temic symptoms (DRESS). Late complications of p-i DHR in clude viral reactivation, autoimmune reactions, multiple drug hypersensitization. Thus, due to these immune stimuli VHS responses are highly unorthodox in both clinic and pathophysiology and are difficult to analyse, predict, and treat.
Methods. Working methods used – searching for relevant literature in PubMed, Medscape, medical databases, and a specialized searchengine Google Scholar.
Conclusion. A review of the literature suggests that non-covalent link ages may affect most aspects of drug hypersensitivity reactions, but more evidence is needed to substantiate the theory.
