Personalized diagnostic approach and indirect quantification of extravasation in human anaphylaxis

Abstract

Background: Anaphylaxis is the most acute and life-threatening manifestation of al lergic disorders. Currently, there is a need to improve its medical management and increase the understanding of its molecular mechanisms. This study aimed to quantify the extravasation underlying human anaphylactic reactions and propose new therag nostic approaches. Methods: Molecular determinations were performed in paired serum samples ob tained during the acute phase and at baseline from patients presenting with hyper sensitivity reactions. These were classified according to their severity as Grades 1, 2 and 3, the two latter being considered anaphylaxis. Tryptase levels were measured by ImmunoCAP, and serum protein concentration was quantified by Bradford assay. Human serum albumin (HSA) and haemoglobin beta subunit (HBB) levels were deter mined by Western blot and polyacrylamide gel electrophoresis, respectively Results: A total of 150 patients were included in the study. Of them, 112 had experi enced anaphylaxis (83 and 29 with Grade 2 and 3 reactions, respectively). Tryptase di agnostic efficiency substantially improved when considering patients' baseline values (33%¿54%) instead of the acute value threshold (21%). Serum protein concentration and HSA significantly decreased in anaphylaxis (p<¿.0001). HSA levels dropped with the severity of the reaction (6% and 15% for Grade 2 and 3 reactions, respectively). Furthermore, HBB levels increased during the acute phase of all hypersensitivity re actions (p<¿.0001). Conclusions: For the first time, the extravasation underlying human anaphylaxis has been evaluated based on the severity of the reaction using HSA and protein concen tration measurements. Additionally, our findings propose new diagnostic and poten tial therapeutic approaches for this pathological event. KEYWORDS anaphylaxis, haemoglobin, human serum albumin, protein concentration, tryptase