CHILDHOOD ANAPHYLAXIS: NEW DEVELOPMENTS IN DIAGNOSIS AND TREATMENT

CHILDHOOD_ANAPHYLAXIS_NEW_DEVELOPMENTS _IN_DIAGNOSIS_AND_TREATMENT_kapak

BIOMARKERS IN ANAPHYLAXIS

Kazım Okan Dolu

Kanuni Sultan Süleyman Training and Research Hospital, Department of Pediatric Immunology and Allergic Diseases, İstanbul, Türkiye

Dolu KO. Biomarkers in Anaphylaxis. In: Harmancı K, editor. Childhood Anaphylaxis: New Developments in Diagnosis and Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.223-238.

ABSTRACT

Anaphylaxis is a rapidly developing, potentially life-threatening systemic hypersensitivity reaction, with diagnosis primarily based on clinical findings. Therefore, acute treatment should not be delayed for laboratory tests. Laboratory tests are often needed in cases where anaphylaxis diagnosis is suspected. Serum total mast cell tryptase is the most frequently used laboratory test in anaphylaxis diagnosis. Tryptase, a neutral serine protease released from mast cells, has significant diagnostic value due to its peak levels occurring 30-120 minutes after reaction onset and its longer half-life (approximately 2 hours) compared to other mediators. However, tryptase levels may vary according to the etiology of anaphylaxis. In food-induced anaphylaxis, tryptase elevation is less pronounced compared to drug and venom-induced cases, and may not increase at all in some patients. Serial measurements and comparison with baseline values are recommended for optimal diagnostic value; specifically, using the formula “peak mast cell tryptase ≥ [1.2 × baseline tryptase + 2 ng/mL]” increases diagnostic accuracy. Histamine and its metabolites (N-methylhistamine, imidazole acetic acid) may be valuable in food-induced anaphylaxis cases where tryptase does not elevate, but histamine’s short half-life (1-2 minutes) and special sample processing requirements limit its clinical use. Platelet activating factor (PAF) shows strong correlation with anaphylaxis severity and is found to be superior to tryptase and histamine in predicting reaction severity. Other biomarkers such as chymase, carboxypeptidase A3, CCL-2, dipeptidyl peptidase I, and basogranulin may offer complementary diagnostic value, especially in situations where tryptase measurement remains negative. MicroRNAs, particularly hsa-miR-451a, miR-21-3p, and miR-487b-3p, emerge as promising new biomarkers in anaphylaxis diagnosis, showing sensitive diagnostic value in both adult and pediatric anaphylaxis cases. Using combinations of multiple biomarkers rather than a single marker can increase sensitivity and specificity, especially when tryptase levels do not elevate. Current clinical guidelines consider measuring and comparing acute and baseline serum tryptase levels more valuable for anaphylaxis diagnosis. The routine clinical use of other biomarkers is limited due to their short half-lives, special sampling requirements, non-standardized analysis platforms, absence of commercialized kits, and lack of sufficiently large prospective validation studies.

Keywords: Anaphylaxis; Biomarkers; Tryptase; Histamine; Platelet-activating factor

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