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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Molecular Innate Immunity

This article is part of the Research TopicCell Models and Preclinical Validation of Immune-Mediating Biological TherapiesView all 9 articles

A Functional Cell Model using Basophil Activation Test to Study Molecular Mechanisms and Biomarkers of Response to Omalizumab Treatment in Patients with Asthma

Provisionally accepted
Boris  GoleBoris Gole1Larisa  GoričanLarisa Goričan1Gregor  JezernikGregor Jezernik1Mario  GorenjakMario Gorenjak1Anja  BizjakAnja Bizjak1Vojko  BerceVojko Berce1,2Maja  Skerbinjek KavalarMaja Skerbinjek Kavalar3Michael  KabeschMichael Kabesch4Erik  MelénErik Melén5Korneliusz  GolebskiKorneliusz Golebski6Cornelius  M van DrunenCornelius M van Drunen6Anke  Hilse Maitland-van der ZeeAnke Hilse Maitland-van der Zee6Susanne  ReinartzSusanne Reinartz7Susanne  J H VijverbergSusanne J H Vijverberg6Uroš  PotočnikUroš Potočnik1,2,8*
  • 1Faculty of Medicine, University of Maribor, Maribor, Slovenia
  • 2Univerzitetni Klinicni Center Maribor, Maribor, Slovenia
  • 3Ambulanta Čebelica, Maribor, Slovenia
  • 4Universitatsklinikum Regensburg, Regensburg, Germany
  • 5Karolinska Institutet, Stockholm, Sweden
  • 6Amsterdam UMC Locatie AMC, Amsterdam, Netherlands
  • 7Tergooi MC, Hilversum, Netherlands
  • 8Univerza v Mariboru Fakulteta za kemijo in kemijsko tehnologijo, Maribor, Slovenia

The final, formatted version of the article will be published soon.

Introduction: Patients with severe asthma may benefit from targeted biological therapies. However, personalized therapy in children and adolescents with asthma, based on individual susceptibility to molecular mechanisms addressed by different biologicals is underdeveloped. Here, we established a functional in vitro model, to study the differential responses of asthma patients to omalizumab (an IgE targeting biological) therapy. Methods: White blood cells isolated from asthmatic children and adolescents were pre-treated with omalizumab. Next, basophil activation and degradation were used to assess the in vitro patient's response to omalizumab after exposure to patient-specific allergens. In parallel, basophils-specific whole RNA sequencing was used to screen for differentially expressed genes associated with an in vitro response to omalizumab. The results of the screen were first confirmed in an independent cohort of patients, and finally compared to the clinically relevant data. Results: The in vitro basophil activation + degradation test may be used to study the differential response to omalizumab in patients. The differentially expressed genes in the basophils of the better vs. the poor/non-responders are associated primarily with defense against viruses. The low RSAD2 expression correlates with poor response to omalizumab in vitro. Conclusions: We describe an in vitro test to study the differential response to omalizumab in patients. RSAD2 may be a biomarker for response to omalizumab in asthma.

Keywords: Basophil activation, biomarker, differential response to omalizumab, in vitro cell model, pediatric asthma, precision medicine, Transcriptomics

Received: 13 Nov 2025; Accepted: 13 Feb 2026.

Copyright: © 2026 Gole, Goričan, Jezernik, Gorenjak, Bizjak, Berce, Skerbinjek Kavalar, Kabesch, Melén, Golebski, van Drunen, Maitland-van der Zee, Reinartz, Vijverberg and Potočnik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Uroš Potočnik

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