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. 2022 Jul 13:3:787749.
doi: 10.3389/falgy.2022.787749. eCollection 2022.

Basophil Activation Test as a Biomarker for Taxanes Anaphylaxis

Lucila De Campos  1   2 , Pedro Giavina-Bianchi  1 , Shree Acharya  2 , Donna-Marie Lynch  2 , Jorge Kalil  1 , Mariana C Castells  2
Affiliations

Basophil Activation Test as a Biomarker for Taxanes Anaphylaxis

Lucila De Campos et al. Front Allergy. .

Abstract

Introduction: Taxanes are widely used chemotherapy agents, and their administration, despite premedication, is associated with hypersensitivity reactions (HR) in up to 9% of patients, 1% of which are severe. The mechanisms of these reactions are not fully understood. Finding biomarkers for early diagnosis and better understanding the underlying mechanisms of these reactions are key to defining the best treatment strategy for patients.

Methods: The purpose of this study was to evaluate the effectiveness of the basophil activation test (BAT) to diagnose patients with anaphylactic reactions to taxanes. Patients with anaphylaxis to taxane compounds (n = 15) were assessed through clinical history, skin testing (when possible), and BAT. BAT was performed immediately before rapid drug desensitization or before skin testing using anti-CD123 conjugated (APC-Biolegend), anti-HLADR conjugated (FITC-Biolegend) to gate Basophils and anti-CD63 conjugated (PE-Biolegend), and anti-CD203c conjugated (BV-Biolegend) to assess CD203c and CD63 expression on basophils under taxane stimulation. BAT was also performed in eight healthy volunteers.

Results: BAT was positive for CD203c in eight out of 15 patients and for CD63 in four out of 15 patients and in two out of eight controls. The sensitivity for CD203c was 53%, the specificity was 87%, and the area under the curve was 0.66 (p = 0.19%). For CD63, these rates were 33%, 87%, and 0.6 (p = 0.4). In a subgroup analysis of patients with positive skin tests (11 patients), CD203c was positive in six patients (sensitivity of 54.5% and specificity of 87.5%), and CD63 was positive in five patients (sensitivity of 45% and specificity of 75%).

Conclusions: BAT as a diagnostic tool for immediate hypersensitivity reactions to taxanes may be relevant in patients with selected phenotypes and endotypes, especially those with severe reactions or when the diagnosis cannot be established by the skin test. Increased expression of CD203c was more frequent than of CD63 in patients with positive results, and the sensitivity of this biomarker was higher in patient sub-group with positive skin tests, i.e., patients with IgE-mediated endotypes.

Keywords: anaphylaxis; basophil activation test (BAT); chemotherapy; immediate hypersensitivity reaction; taxanes agents.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Positive Basophil Activation test. Increased MFI after basophil stimulation with paclitaxel compared with negative control (PBS).
Figure 2
Figure 2
ROC curve: stimulation index for CD63 expression after stimulation with paclitaxel 1:10 vs. saline CD63: Threshold > 1.8; sensitivity 33% and specificity 88%.
Figure 3
Figure 3
Graphic representation of the Stimulation index from the CD63 and CD203c expression in patients and controls after basophil activation with taxanes. Cut-off for CD203c 1.3 and for CD63 1.8.
See this image and copyright information in PMC

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