HMGB1-RAGE, A Useful Partnership in Vital Response?

Abstract Introduction: In forensic practice, it is well known that the mechanism and dating of traumatic injuries is one of the primary responsibilities of this specialty. Currently, it is a subject still debated by researchers, and so far, an infallible marker that would objectively support their intravitam/postmortem occurrence has not yet been identified. However, studies have shown that the HMGB1-RAGE axis is rapidly activated after trauma and might be an essential element to help solve the forensic problem of wound dating. Purpose: To compare the values of HMGB1-RAGE expression occurring in wounds produced intravitally shortly before death and in wounds produced postmortem and to quantify the differences arising between them. Material and method: For this prospective study, skin fragments were collected from the site of wounds in autopsied cadavers at the County Clinical Service of Forensic Medicine Constanta (SCJML Constanta), wounds produced intravitally and with a maximum survival time of 60 minutes. Postmortem wounds and control fragments from volunteers undergoing surgery for skin tumours were also collected. The main conditions were: chronological documentation of the lesion and absence of neoplastic or inflammatory conditions. Ninety-six autopsy cases between 2021–2022 met the criteria for inclusion in the study. A control fragment accompanied each fragment from the wound. Routine Hematoxylin-Eosin (HE), Perls and Van Gieson Werhoeffstaining, as well as immunohistochemistry with HMGB1 and RAGE markers were performed on each fragment and a score based on staining intensity was determined. Results: Routine staining was not useful in assessing vitality in segments with survival time up to 30 min. Immunohistochemically, both markers showed increased values compared to control values (p<0.0001) and to lesions produced postmortem. An interesting aspect is the lack of reactivity in the lesion’s margins for both markers. Conclusions: Although further research is needed, the results of our study support the hypothesis that the HMGB1-RAGE axis is useful in assessing the vital reaction in skin wounds.