Erroneous detection of desensitization doses in the prevention of hypersensitivity reactions.

Background: Desensitization protocols have empirically established their efficacy and safety in eliminating most of the hypersensitivity reactions to drugs and other allergens. Without such procedures, the offending drugs can otherwise be lethal, for some patients, when singularly administered at therapeutic doses. These binding events and the subsequent signaling cascades have been extensively modulated by different desensitization methods, without any clear explanation as to why it is necessary to use increasing allergen doses.

Fever temperatures modulate intraprotein dynamics and enhance the binding affinity between monoclonal antibodies and the spike protein from SARS-CoV-2.

Fever is a typical symptom of most infectious diseases. While prolonged fever may be clinically undesirable, mild reversible fever (<39℃, 312 K) can potentiate the immune responses against pathogens. Here, using molecular dynamics and free energy calculations, we investigated the effect of febrile temperatures (38℃ to 40℃, 311 K to 313 K) on the immune complexes formed by the SARS-CoV-2 spike protein with two neutralizing monoclonal antibodies.

Temporal Modulation of Drug Desensitization Procedures.

Drug hypersensitivity reactions are an unavoidable clinical consequence of the presence of new therapeutic agents. These adverse reactions concern patients afflicted with infectious diseases (e.g.

Fever as an evolutionary agent to select immune complexes interfaces.

We herein analyzed all available protein-protein interfaces of the immune complexes from the Protein Data Bank whose antigens belong to pathogens or cancers that are modulated by fever in mammalian hosts. We also included, for comparison, protein interfaces from immune complexes that are not significantly modulated by the fever response. We highlight the distribution of amino acids at these viral, bacterial, protozoan and cancer epitopes, and at their corresponding paratopes that belong strictly to monoclonal antibodies.