Anaphylaxis is a serious, systemic acute allergic reaction that occurs due to various triggers and through a variety of mechanisms. Measurement of serum mast cell tryptase is currently the most commonly used laboratory test, but has many limitations. In our study, we focused on potential new diagnostic biomarkers of anaphylaxis that are more basophil- than mast cell-related. We included a total of 204 anaphylactic patients who were presented to the Emergency Department of University Clinic Golnik in the time frame from January 2011 to December 2018. Paired serum samples were collected: in acute phase during the reaction and later in basal state (approximately 1 month after the reaction). The most common trigger of reactions was Hymenoptera venom and most patients suffered the worst, Mueller's IV grade of reaction. A total of 203 healthy controls were included for comparison. The results showed, that during anaphylaxis, among 11 selected chemokines, there is a significant increase in C-C Motif Chemokine Ligand 2 (CCL2) only, and its concentration and the percentage change from baseline values are both related to the reaction severity. CCL2 strongly correlates with tryptase, and an increase in CCL2 was present also in 30 % of those patients in whom tryptase levels were not elevated. During anaphylaxis, there is a significant decrease in the absolute number of basophils and, consequently, a decrease in relative gene expression of all three basophil markers; the α-subunit of the high-affinity IgE receptor FcεRI (FCER1A), carboxypeptidase A3 (CPA3) and L-histidine decarboxylase (HDC). Additionally, significant decrease is also observed in C-C Motif Chemokine Receptor 2 (CCR2) on the surface of basophils and in the proportion of CCR2 positive cells. These results support the hypothesis of potential basophil migration during an anaphylactic reaction from blood to the site of inflammation. In vitro whole blood stimulations showed lower CCR2 receptors on basophils surface and unchanged concentrations of CCL2 in plasma, suggesting that activated basophils in patients with previously known acute allergic reactions history, do not produce de novo and secrete elevated levels of CCL2 as a response to re-stimulation with the same allergen. We can conclude that basophil-related biomarkers, in addition to mast cell tryptase, represent new potential (and additional) diagnostic biomarkers of anaphylaxis.
|
