Positive CD63 Basophil Activation Tests Are Common in Children with Chronic Spontaneous Urticaria and Linked to High Disease Activity

Abstract

Background: The basophil activation test (BAT) using CD63 expression is a sensitive and specific tool for the diagnostic workup of autoimmune chronic spontaneous urticaria (CSU). The definition of a positive BAT is directly dependent on the reference range and the cutoff values established in control populations. As of now, the pediatric reference range and cutoff values of the CD63 BAT remain to be established. Methods: In this study, we analyzed CD63 expression in 80 children (1-17 years old) without chronic urticaria (i.e., controls) and compared the values to those of a pediatric cohort of 105 CSU patients and 23 physical urticaria (PU) patients. Results: Based on the log-normal distribution of CD63 values in control subjects, the reference range and the cutoff for positive CD63 BAT values was established to be 1.2-1.8% (95% CI) and 1.8%, respectively. Children with CSU showed significantly elevated and significantly increased BAT values compared to healthy controls (Wilcoxon rank test p value <0.001). In contrast, no difference was found between BAT results in controls and PU patients. In pediatric CSU patients, a higher disease activity was associated with higher BAT values. Conclusions: Our study provides, for the first time, reference and cutoff values for the CD63 BAT in children. Our findings show that positive CD63 BAT are common in children with CSU and linked to a high disease activity.

Effective management of severe cutaneous mastocytosis in young children with omalizumab (Xolair® )

“…Tryptase blood levels are considered to be a selective marker of mast cell activation, 4 while tetraspanin (CD63) is a cell surface marker that is upregulated on degranulating basophils and mast cells, and can be measured by flow cytometry. 5,6 There were no substantial changes in tryptase/CD63 5 levels assessed at the same time (tryptase 40-35 lg/L and CD63 1.8-1.7%; normal range < 1.8% 5 ). The patient was asymptomatic without disease flares within 1 month following treatment initiation.…”

“…In addition, we assessed changes in the levels of two biomarkers related to mast cell activation: tryptase and CD63. Tryptase blood levels are considered to be a selective marker of mast cell activation, while tetraspanin (CD63) is a cell surface marker that is upregulated on degranulating basophils and mast cells, and can be measured by flow cytometry . There were no substantial changes in tryptase/CD63 levels assessed at the same time (tryptase 40–35 μg/L and CD63 1.8–1.7%; normal range < 1.8%).…”

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria

“…BATs assess histamine release or upregulation of activation markers of donor basophils in response to stimulation with the serum of CSU patients. BATs can help to co‐assess disease activity in patients with urticaria as well as to diagnose autoimmune urticaria . Furthermore, BAT can be used as a marker for responsiveness to ciclosporin A or omalizumab …”

Urticaria in children and adolescents: An updated review of the pathogenesis and management

“…The detection of autoantibodies in children does not affect the prognosis . Recently, it was found that positive CD63 basophil activation test is common in PcsU and is associated with high disease activity . Low blood basophil counts on the contrary were linked to earlier symptoms resolution …”