Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 30:S0091-6749(25)00702-X.
doi: 10.1016/j.jaci.2025.05.032. Online ahead of print.

Exploring geographic differences in IgE response through network and manifold analyses

Alex Cucco  1 , Neil Pearce  2 , Angela Simpson  3 , Lucy Pembrey  2 , Harriet Mpairwe  4 , Camila A Figueiredo  5 , Philip J Cooper  6 , Jeroen Douwes  7 , Collin Brooks  7 , Ian M Adcock  8 , Nazanin Zounemat Kermani  8 , Graham D M Roberts  9 , Clare S Murray  3 , Adnan Custovic  10 , Sara Fontanella  8 ; WASP Study Group; STELAR/UNICORN Consortium; U-BIOPRED Consortium
Collaborators, Affiliations
Free article

Exploring geographic differences in IgE response through network and manifold analyses

Alex Cucco et al. J Allergy Clin Immunol. .
Free article

Abstract

Background: Component-resolved diagnostics allow detailed assessment of IgE sensitization to multiple allergenic molecules (component-specific IgEs, or c-sIgEs) and may be useful for asthma diagnosis. However, to effectively use component-resolved diagnostics across diverse settings, it is crucial to account for geographic differences.

Objective: We investigated spatial determinants of c-sIgE networks to facilitate development of diagnostic algorithms applicable globally.

Methods: We used multiplex component-resolved diagnostics array to measure c-sIgE to 112 proteins in an international collaboration of several studies: WASP (World Asthma Phenotypes; United Kingdom, New Zealand, Brazil, Ecuador, and Uganda), U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes; 7 European countries), and MAAS (Manchester Asthma and Allergy Study, a UK population-based birth cohort). Hierarchical clustering on low-dimensional representation of co-occurrence networks ascertained sensitization and c-sigE clusters across populations. Cross-country comparisons focused on a common subset of 18 c-sIgEs. We investigated sensitization networks across regions in relation to asthma severity.

Results: Sensitization profiles shared similarities across regions. For 18 c-sIgEs shared across study populations, the response structure enabled differentiation between different geographic areas and study designs, revealing 3 clusters: (1) Uganda, Ecuador, and Brazil, (2) U-BIOPRED children and adults, and (3) New Zealand, United Kingdom, and MAAS. Spectral clustering identified differences between clusters. We observed constant, almost parallel shifts between severe and nonsevere asthma in each country.

Conclusions: Patterns of c-sIgE response reflect geographic location and study design. However, despite geographic differences in c-sIgE networks, there is a remarkably consistent shift between networks of subjects with nonsevere and severe asthma.

Keywords: Asthma; allergic sensitization; asthma diagnosis; cluster; component-resolved diagnostics; network analysis; statistical network analysis.

PubMed Disclaimer

Conflict of interest statement

Disclosure statement A.C. was funded through the Meaningful Dragon PhD scholarship. MAAS is supported by Asthma UK grants 301 (1995-1998), 362 (1998-2001), 01/012 (2001-2004), and 04/014 (2004-2007), BMA James Trust (2005), and the J. P. Moulton Charitable Foundation (2004-2016), The North West Lung Centre Charity (1997-current), and Medical Research Council grant MR/L012693/1 (2014-2018). Infrastructure support for this research was provided by the Imperial and Manchester National Institute for Health Research (NIHR) Imperial Biomedical Research Centres. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. U-BIOPRED is supported through an Innovative Medicines Initiative Joint Undertaking under grant 115010, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations companies’ in-kind contribution (www.imi.europa.eu). The WASP collaboration is based on the Asthma Phenotypes study, which is funded by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grants 668954 and 101020088. The UK Medical Research Council and Wellcome (21706/Z/19/Z) and the University of Bristol provide core support for ALSPAC. Disclosure of potential conflict of interest: A. Custovic reports personal fees from Novartis, Sanofi, Stallergenes Greer, La Roche-Posay, and Reacta Healthcare outside the submitted work. A. Simpson reports lecture fees from Thermo Fisher Scientific. The rest of the authors declare that they have no relevant conflicts of interest.

LinkOut - more resources