Siglec-8 as a Biomarker for Predicting Anti-IL-5 Response in Severe Asthma

초록

Purpose: Biologic therapies have revolutionized the management of severe asthma (SA), yet the variability in patient responses necessitates identification/verification of predictive biomarkers. Siglec-8, a sialic acid-binding immunoglobulin-like lectin 8 selectively that is expressed on eosinophils, could serve as a biomarker for predicting responsiveness to biologics in patients with SA. It is necessary to evaluate the predictive value of baseline serum Siglec-8 levels compared to other parameters, including blood eosinophil counts, in determining clinical responses to anti-interleukin 5 (IL-5) therapies in patients with SA. Methods: This study included 68 patients with SA from the Precision Medicine Intervention in Severe Asthma study, who had initiated anti-IL-5 therapies and whose baseline serum Siglec-8 levels were measured. Clinical outcomes were assessed at 6 and 12 months following treatment. Excellent responders were defined as patients with zero exacerbations during follow-up. Multivariable logistic regression and receiver operating characteristic curve analyses were performed to compare the predictive performance of serum Siglec-8 levels versus that of other parameters. Results: Data from 29 patients treated with mepolizumab and 39 patients treated with reslizumab were analyzed. Baseline serum Siglec-8 levels showed a trend toward better diagnostic performance compared to blood eosinophil counts for predicting 6- and 12-month clinical responses (area under the curve, 0.931 vs. 0.836; P = 0.08 for 6-month responders; and 0.811 vs. 0.628, P = 0.05 for 12-month excellent responders). Additionally, the ratio of serum Siglec-8 levels to blood eosinophil counts significantly increased after 6 months of anti-IL-5 therapy (P < 0.001). Conclusions: Baseline serum Siglec-8 levels showed a trend toward better predictive performance than other parameters for predicting 6- and 12-month responses to anti-IL-5 therapies in patients with SA. These findings suggest that Siglec-8 may have the potential as a biomarker for guiding treatment decisions, although further validation in larger, prospective studies is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT05164939 © 2025 The Korean Academy of Asthma, Allergy and Clinical Immunology. The Korean Academy of Pediatric Allergy and Respiratory Disease. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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