Postmortem detection of antibiotic-specific immunoglobulin E in the case of anaphylactic death

An allergic anaphylactic reaction is a potentially fatal cascade consisting of an initial sensitization, antigen exposure, crosslinking of immunoglobulin E (IgE) specific for the antigen, activation of mast cells, and release of bioactive substances. Postmortem diagnosis of anaphylaxis is challenging because of the limited availability of antemortem history and minimal macroscopic evidence at autopsy. The elevated activity of a neutral proteinase, such as tryptase, can be a surrogate marker for the activation and degranulation of mast cells. However, it does not directly indicate the involvement of antigen-specific IgE, which has an important role in IgE-mediated allergic anaphylaxis. In the present study, we examined blood from a case of death following infusion of the antibiotic ceftriaxone (CTRX), with a control case for comparison. The aim was to detect IgE specific for CTRX. A pull-down assay with N-hydroxysuccinimide-activated sepharose identified IgE specific for CTRX only in the serum obtained from the case of CTRX exposure, and not in the control case. The specificity of IgE was confirmed by adsorption to an excess of CTRX, which resulted in the signal for IgE disappearing in the pull-down assay. This antigen-specific IgE is a key molecule in the IgE-mediated allergic anaphylaxis and seldom investigated in postmortem examinations. Its detection can provide support for the postmortem diagnosis of allergic anaphylaxis, especially when combined with an antemortem history of allergen exposure and elevated neutral proteinase levels in serum.