. 2024 Jun 11;17(6):100904. doi: 10.1016/j.waojou.2024.100904

Table 2.

Potential biomarkers in anaphylaxis.

Potential biomarkers	Evidence
Total tryptase (pro, pro’, and mature forms of α/β tryptases)⁸⁵^,87, 88, 89, 90, 91, 92, 93^,⁹⁸	• Tryptase is a serine protease. The alpha form is passively secreted and the beta form is predominantly present in secretory granules of mast cells and basophils • Half-life approximately 2 h • Peaks within 60–90 min after symptom onset but can persist for 6 h • Blood sample should optimally be obtained within 3 h of onset of anaphylaxis symptoms • Elevation of the acute total tryptase level of 20% + 2 ng/L above a baseline is an indicative of a significant mast cell degranulation event • Consider comparing the level measured during the acute event with a baseline level (obtained 24 h after resolution of the acute event) or on stored serum, if available (levels are stable for at least 1 year in stored frozen sera) • If higher in acute serum than in baseline serum, a diagnosis of anaphylaxis is likely • If elevated (≥20 ng/mL) in both acute and baseline sera, the diagnosis of mastocytosis should be considered. • The diagnosis of HαT may be considered in patients with basal tryptase level >8 ng/mL and a history of severe allergic events • If within normal limits in a blood sample taken during anaphylaxis, the diagnosis of anaphylaxis cannot be excluded • Total tryptase level can be measured in postmortem serum (blood samples preferably obtained from femoral vessels rather than the heart; the level needs to be correlated with the clinical history) • High concentration of alpha-tryptase has been observed in patients with systemic mastocytosis, a clonal disorder associated with mutation of the membrane tyrosine kinase KIT, and the concentration of beta-tryptase was increased during anaphylactic reactions • Serum tryptase level may be a noninvasive, promising prognostic long-term biomarker in patients with ACS, STEMI and non-STEMI • In challenges to hymenoptera venom, tryptase concentration has been correlated with severity of anaphylaxis after a sting • Significant increase in baseline tryptase level with increasing age
IgE against Galactose-α−1,3-galactose (alpha-gal)⁸⁶^,⁹⁴^,⁹⁶^,⁹⁷	• May cause red meat anaphylaxis • Responsible for delayed form of anaphylaxis occurring 3–6 h after ingestion of red meat • Independently associated with noncalcified plaque burden and obstructive coronary artery disease. It is also associated with ST-segment–elevated myocardial infarction.
Plasma angiotensin II⁸⁶^,⁹⁹	• Synthesized from angiotensin I by ACE • Normal of serum ACE is 20–70 U/L, but the range varies by age and genotype • Low ACE levels have been found in patients with severe anaphylaxis as assessed by cardiovascular collapse and airway angioedema • May play a role for measurement of the renin-angiotensin system to understand the pre-existing level of risk of severe anaphylaxis • Lower levels of angiotensinogen, angiotensin I and II have been reported in patients with hymenoptera anaphylaxis versus normal controls, and the levels were even lower in patients with severe anaphylaxis
Platelet-activating factor⁸⁷^,⁹⁸^,¹⁰⁰^,102, 103, 104^,¹¹¹	• Important mediator in anaphylaxis • Secreted by mast cells, basophils, leukocytes, fibroblasts, endothelial cells neutrophils, eosinophils, platelets, and cardiac muscle cells • Short half-life of 3–13 min when associated with low PAF-AH • Increased concentrations of PAF in plasma during an acute allergic reaction in children and adults • PAF concentration correlates very well with the severity of an anaphylactic reaction • PAF and CRD plays an important role in anaphylaxis caused by peanuts
Chymase⁸⁵^,⁸⁷^,⁹⁸	• Normal level: chymase <3 ng/mL • Predominantly found in mast cells, potentially stable in serum • Unknown half-life • Elevated chymase level reported hours after anaphylactic death
Carboxypeptidase A₃⁸⁵^,⁸⁷^,⁹⁸	• Normal level: carboxypeptidase A₃ <14 ng/mL • Potentially detectable in serum and saliva; limited data suggests a rise in anaphylaxis where MCT is not elevated • Half-life longer than tryptase and this may potentially be an advantage if sampling time >2 h from onset of symptoms
Cathepsin G (dipeptidyl peptidase I)⁸⁵^,⁹⁸	• Unknown half-life • Non-specific biomarker– expressed in many other cells • Elevation of cathepsin G level might correlate with severity scores during food challenge
Prostaglandin F2¹⁰⁶	• Is a prostaglandin D2 metabolite • Increase in urinary prostaglandin F2 levels suggest mast cell activation in wine-induced asthma
Other inflammatory mediators⁹⁵^,¹⁰³^,¹⁰⁷^,¹⁰⁸	• Serum inflammatory mediators such as IL-2, IL-6, IL-10, TNF receptor 1 have been shown to be elevated in blood during severe anaphylaxis • IL-6 has been found to correlate with severity of anaphylaxis • Due to shorter half-life, leukotrienes are difficult to measure in the blood • Increased LTE₄ are associated with anaphylaxis • Histamine can be a useful indicator of mast cell activity/degranulation but requires cold and rapid processing (including centrifugation) as it rapidly degrades

ACS, acute coronary syndrome; ACE, angiotensin-converting enzyme; IgE, immunoglobin; IL, interleukin;, hereditary alpha tryptasemia; LTE, leukotriene; MCT, mast cell tryptase; TNF, tumor necrosis factor; PAF, platelet-activating factor; PAF-AH, PAF-acetylhydrolase; STEMI, ST-elevation myocardial infarction.