Post mortem determination of (β)-tryptase for the diagnosis of anaphylaxis: Looking for a reasonable cut-off

Anaphylactic deaths represent a critical issue for forensic pathologists and its post-mortem diagnosis requires several steps in order to formulate a correct and reliable diagnosis, which is not always reachable in a forensic setting. This is the reason why, especially in deaths occurred out-of-hospital or in an unclear accidental manner, reliable diagnostic methods to confirm or exclude anaphylaxis would be of great value. Mast cells are the main effectors of anaphylaxis, they are present throughout the body, but more abundant in the skin and around blood vessels, in the respiratory and intestinal mucosa, and in connective tissue. The content of granules contained into mast cells is excreted when these cells are stimulated; one of the components stored in granules is the neutral protease, tryptase. Tryptase exists in two isoforms, α and β; α-tryptase is constantly secreted from mast cells as an inactive pro-enzyme and it is used to quantify mast cells, the other isoform, β-tryptase, is activated through two proteolytic phases: the first phase occurs at acidic pH and when heparin or dextran sulphate are present and it includes an autocatalytic intermolecular cleavage, generating a monomer, significantly less active than the final tetramer. In the second phase following the removal of the remaining precursor dipeptide by dipeptidyl peptidase I, there will be the formation of the active tetramer.