Exploring geographic differences in IgE response through network and manifold analyses

Alex Cucco; Neil Pearce; Angela Simpson; Lucy Pembrey; Harriet Mpairwe; Camila A. Figueiredo; Philip J. Cooper; Jeroen Douwes; Collin Brooks; Ian M. Adcock; Nazanin Zounemat Kermani; Graham D. M. Roberts; Clare S. Murray; Adnan Custovic; Sara Fontanella; Stephen Turner; John W. Holloway; Syed Hasan Arshad; John A. Curtin; Ashley Woodcock; Raquel Granell; Andrew Bush; Sejal Saglani; H. Ahmed; C. Auffray; P. Bakke; A. T. Bansal; F. Baribaud; S. Bates; E. H. Bel; J. Bigler; H. Bisgaard; M. J. Boedigheimer; K. Bønnelykke; J. Brandsma; P. Brinkman; E. Bucchioni; D. Burg; A. Bush; M. Caruso; A. Chaiboonchoe; P. Chanez; F. K. Chung; C. H. Compton; J. Corfield; A. D'Amico; B. Dahlén; S. E. Dahlén; B. de Meulder; R. Djukanovic; V. J. Erpenbeck; D. Erzen; K. Fichtner; N. Fitch; L. J. Fleming; E. Formaggio; S. J. Fowler; U. Frey; M. Gahlemann; T. Geiser; V. Goss; Y. Guo; S. Hashimoto; J. Haughney; G. Hedlin; P. W. Hekking; T. Higenbottam; J. M. Hohlfeld; C. Holweg; I. Horváth; P. Howarth; A. J. James; R. G. Knowles; A. J. Knox; N. Krug; D. Lefaudeux; M. J. Loza; R. Lutter; A. Manta; S. Masefield; J. G. Matthews; A. Mazein; A. Meiser; R. J. M. Middelveld; M. Miralpeix; P. Montuschi; N. Mores; J. Musial; D. Myles; L. Pahus; I. Pandis; S. Pavlidis; A. Postle; P. Powel; G. Praticò; M. Puig Valls; N. Rao; J. Riley; A. Roberts; A. Rowe; T. Sandström; J. P. R. Schofield; W. Seibold; A. Selby; D. E. Shaw; R. Sigmund; F. Singer; P. J. Skipp; A. R. Sousa; P. J. Sterk; K. Sun; W. M. van Aalderen; B. Thornton; M. van Geest; J. Vestbo; N. H. Vissing; A. H. Wagener; S. S. Wagers; Z. Weiszhart; C. E. Wheelock; S. J. Wilson

doi:10.1016/j.jaci.2025.05.032

Exploring geographic differences in IgE response through network and manifold analyses

Alex Cucco
, Neil Pearce
, Angela Simpson
, Lucy Pembrey
, Harriet Mpairwe
, Camila A. Figueiredo
, Philip J. Cooper
, Jeroen Douwes
, Collin Brooks
, Ian M. Adcock
, Nazanin Zounemat Kermani
, Graham D. M. Roberts
, Clare S. Murray
, Adnan Custovic^*
, Sara Fontanella
, Stephen Turner
, John W. Holloway
, Syed Hasan Arshad
, John A. Curtin
, Ashley Woodcock

Raquel Granell, Andrew Bush, Sejal Saglani, H. Ahmed, C. Auffray, P. Bakke, A. T. Bansal, F. Baribaud, S. Bates, E. H. Bel, J. Bigler, H. Bisgaard, M. J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, F. K. Chung, C. H. Compton, J. Corfield, A. D'Amico, B. Dahlén, S. E. Dahlén, B. de Meulder, R. Djukanovic, V. J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L. J. Fleming, E. Formaggio, S. J. Fowler, U. Frey, M. Gahlemann, T. Geiser, V. Goss, Y. Guo, S. Hashimoto, J. Haughney, G. Hedlin, P. W. Hekking, T. Higenbottam, J. M. Hohlfeld, C. Holweg, I. Horváth, P. Howarth, A. J. James, R. G. Knowles, A. J. Knox, N. Krug, D. Lefaudeux, M. J. Loza, R. Lutter, A. Manta, S. Masefield, J. G. Matthews, A. Mazein, A. Meiser, R. J. M. Middelveld, M. Miralpeix, P. Montuschi, N. Mores, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, A. Postle, P. Powel, G. Praticò, M. Puig Valls, N. Rao, J. Riley, A. Roberts, A. Rowe, T. Sandström, J. P. R. Schofield, W. Seibold, A. Selby, D. E. Shaw, R. Sigmund, F. Singer, P. J. Skipp, A. R. Sousa, P. J. Sterk, K. Sun, W. M. van Aalderen, B. Thornton, M. van Geest, J. Vestbo, N. H. Vissing, A. H. Wagener, S. S. Wagers, Z. Weiszhart, C. E. Wheelock, S. J. Wilson

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	262-272
Number of pages	11
Journal	Journal of allergy and clinical immunology
Volume	157
Issue number	1
Early online date	2025
DOIs	https://doi.org/10.1016/j.jaci.2025.05.032
Publication status	Published - Jan 2026

Keywords

Asthma
allergic sensitization
asthma diagnosis
cluster
component-resolved diagnostics
network analysis
statistical network analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaci.2025.05.032

Exploring-geographic-differences-in-ige-response-through-network-and-manifold-analyses.pdfFinal published version, 15 MBLicence: CC BY

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Cucco, A., Pearce, N., Simpson, A., Pembrey, L., Mpairwe, H., Figueiredo, C. A., Cooper, P. J., Douwes, J., Brooks, C., Adcock, I. M., Kermani, N. Z., Roberts, G. D. M., Murray, C. S., Custovic, A., Fontanella, S., Turner, S., Holloway, J. W., Arshad, S. H., Curtin, J. A., ... Wilson, S. J. (2026). Exploring geographic differences in IgE response through network and manifold analyses. Journal of allergy and clinical immunology, 157(1), 262-272. https://doi.org/10.1016/j.jaci.2025.05.032

@article{16ea7f11d8ab4526a54b48e50b497b09,

title = "Exploring geographic differences in IgE response through network and manifold analyses",

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",

author = "Alex Cucco and Neil Pearce and Angela Simpson and Lucy Pembrey and Harriet Mpairwe and Figueiredo, \{Camila A.\} and Cooper, \{Philip J.\} and Jeroen Douwes and Collin Brooks and Adcock, \{Ian M.\} and Kermani, \{Nazanin Zounemat\} and Roberts, \{Graham D. M.\} and Murray, \{Clare S.\} and Adnan Custovic and Sara Fontanella and Stephen Turner and Holloway, \{John W.\} and Arshad, \{Syed Hasan\} and Curtin, \{John A.\} and Ashley Woodcock and Raquel Granell and Andrew Bush and Sejal Saglani and H. Ahmed and C. Auffray and P. Bakke and Bansal, \{A. T.\} and F. Baribaud and S. Bates and Bel, \{E. H.\} and J. Bigler and H. Bisgaard and Boedigheimer, \{M. J.\} and K. B{\o}nnelykke and J. Brandsma and P. Brinkman and E. Bucchioni and D. Burg and A. Bush and M. Caruso and A. Chaiboonchoe and P. Chanez and Chung, \{F. K.\} and Compton, \{C. H.\} and J. Corfield and A. D'Amico and B. Dahl{\'e}n and Dahl{\'e}n, \{S. E.\} and \{de Meulder\}, B. and R. Djukanovic and Erpenbeck, \{V. J.\} and D. Erzen and K. Fichtner and N. Fitch and Fleming, \{L. J.\} and E. Formaggio and Fowler, \{S. J.\} and U. Frey and M. Gahlemann and T. Geiser and V. Goss and Y. Guo and S. Hashimoto and J. Haughney and G. Hedlin and Hekking, \{P. W.\} and T. Higenbottam and Hohlfeld, \{J. M.\} and C. Holweg and I. Horv{\'a}th and P. Howarth and James, \{A. J.\} and Knowles, \{R. G.\} and Knox, \{A. J.\} and N. Krug and D. Lefaudeux and Loza, \{M. J.\} and R. Lutter and A. Manta and S. Masefield and Matthews, \{J. G.\} and A. Mazein and A. Meiser and Middelveld, \{R. J. M.\} and M. Miralpeix and P. Montuschi and N. Mores and J. Musial and D. Myles and L. Pahus and I. Pandis and S. Pavlidis and A. Postle and P. Powel and G. Pratic{\`o} and \{Puig Valls\}, M. and N. Rao and J. Riley and A. Roberts and A. Rowe and T. Sandstr{\"o}m and Schofield, \{J. P. R.\} and W. Seibold and A. Selby and Shaw, \{D. E.\} and R. Sigmund and F. Singer and Skipp, \{P. J.\} and Sousa, \{A. R.\} and Sterk, \{P. J.\} and K. Sun and \{van Aalderen\}, \{W. M.\} and B. Thornton and \{van Geest\}, M. and J. Vestbo and Vissing, \{N. H.\} and Wagener, \{A. H.\} and Wagers, \{S. S.\} and Z. Weiszhart and Wheelock, \{C. E.\} and Wilson, \{S. J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2026",

month = jan,

doi = "10.1016/j.jaci.2025.05.032",

language = "English",

volume = "157",

pages = "262--272",

journal = "Journal of allergy and clinical immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "1",

}

Cucco, A, Pearce, N, Simpson, A, Pembrey, L, Mpairwe, H, Figueiredo, CA, Cooper, PJ, Douwes, J, Brooks, C, Adcock, IM, Kermani, NZ, Roberts, GDM, Murray, CS, Custovic, A, Fontanella, S, Turner, S, Holloway, JW, Arshad, SH, Curtin, JA, Woodcock, A, Granell, R, Bush, A, Saglani, S, Ahmed, H, Auffray, C, Bakke, P, Bansal, AT, Baribaud, F, Bates, S, Bel, EH, Bigler, J, Bisgaard, H, Boedigheimer, MJ, Bønnelykke, K, Brandsma, J, Brinkman, P, Bucchioni, E, Burg, D, Bush, A, Caruso, M, Chaiboonchoe, A, Chanez, P, Chung, FK, Compton, CH, Corfield, J, D'Amico, A, Dahlén, B, Dahlén, SE, de Meulder, B, Djukanovic, R, Erpenbeck, VJ, Erzen, D, Fichtner, K, Fitch, N, Fleming, LJ, Formaggio, E, Fowler, SJ, Frey, U, Gahlemann, M, Geiser, T, Goss, V, Guo, Y, Hashimoto, S, Haughney, J, Hedlin, G, Hekking, PW, Higenbottam, T, Hohlfeld, JM, Holweg, C, Horváth, I, Howarth, P, James, AJ, Knowles, RG, Knox, AJ, Krug, N, Lefaudeux, D, Loza, MJ, Lutter, R, Manta, A, Masefield, S, Matthews, JG, Mazein, A, Meiser, A, Middelveld, RJM, Miralpeix, M, Montuschi, P, Mores, N, Musial, J, Myles, D, Pahus, L, Pandis, I, Pavlidis, S, Postle, A, Powel, P, Praticò, G, Puig Valls, M, Rao, N, Riley, J, Roberts, A, Rowe, A, Sandström, T, Schofield, JPR, Seibold, W, Selby, A, Shaw, DE, Sigmund, R, Singer, F, Skipp, PJ, Sousa, AR, Sterk, PJ, Sun, K, van Aalderen, WM, Thornton, B, van Geest, M, Vestbo, J, Vissing, NH, Wagener, AH, Wagers, SS, Weiszhart, Z, Wheelock, CE & Wilson, SJ 2026, 'Exploring geographic differences in IgE response through network and manifold analyses', Journal of allergy and clinical immunology, vol. 157, no. 1, pp. 262-272. https://doi.org/10.1016/j.jaci.2025.05.032

TY - JOUR

T1 - Exploring geographic differences in IgE response through network and manifold analyses

AU - Cucco, Alex

AU - Pearce, Neil

AU - Simpson, Angela

AU - Pembrey, Lucy

AU - Mpairwe, Harriet

AU - Figueiredo, Camila A.

AU - Cooper, Philip J.

AU - Douwes, Jeroen

AU - Brooks, Collin

AU - Adcock, Ian M.

AU - Kermani, Nazanin Zounemat

AU - Roberts, Graham D. M.

AU - Murray, Clare S.

AU - Custovic, Adnan

AU - Fontanella, Sara

AU - Turner, Stephen

AU - Holloway, John W.

AU - Arshad, Syed Hasan

AU - Curtin, John A.

AU - Woodcock, Ashley

AU - Granell, Raquel

AU - Bush, Andrew

AU - Saglani, Sejal

AU - Ahmed, H.

AU - Auffray, C.

AU - Bakke, P.

AU - Bansal, A. T.

AU - Baribaud, F.

AU - Bates, S.

AU - Bel, E. H.

AU - Bigler, J.

AU - Bisgaard, H.

AU - Boedigheimer, M. J.

AU - Bønnelykke, K.

AU - Brandsma, J.

AU - Brinkman, P.

AU - Bucchioni, E.

AU - Burg, D.

AU - Bush, A.

AU - Caruso, M.

AU - Chaiboonchoe, A.

AU - Chanez, P.

AU - Chung, F. K.

AU - Compton, C. H.

AU - Corfield, J.

AU - D'Amico, A.

AU - Dahlén, B.

AU - Dahlén, S. E.

AU - de Meulder, B.

AU - Djukanovic, R.

AU - Erpenbeck, V. J.

AU - Erzen, D.

AU - Fichtner, K.

AU - Fitch, N.

AU - Fleming, L. J.

AU - Formaggio, E.

AU - Fowler, S. J.

AU - Frey, U.

AU - Gahlemann, M.

AU - Geiser, T.

AU - Goss, V.

AU - Guo, Y.

AU - Hashimoto, S.

AU - Haughney, J.

AU - Hedlin, G.

AU - Hekking, P. W.

AU - Higenbottam, T.

AU - Hohlfeld, J. M.

AU - Holweg, C.

AU - Horváth, I.

AU - Howarth, P.

AU - James, A. J.

AU - Knowles, R. G.

AU - Knox, A. J.

AU - Krug, N.

AU - Lefaudeux, D.

AU - Loza, M. J.

AU - Lutter, R.

AU - Manta, A.

AU - Masefield, S.

AU - Matthews, J. G.

AU - Mazein, A.

AU - Meiser, A.

AU - Middelveld, R. J. M.

AU - Miralpeix, M.

AU - Montuschi, P.

AU - Mores, N.

AU - Musial, J.

AU - Myles, D.

AU - Pahus, L.

AU - Pandis, I.

AU - Pavlidis, S.

AU - Postle, A.

AU - Powel, P.

AU - Praticò, G.

AU - Puig Valls, M.

AU - Rao, N.

AU - Riley, J.

AU - Roberts, A.

AU - Rowe, A.

AU - Sandström, T.

AU - Schofield, J. P. R.

AU - Seibold, W.

AU - Selby, A.

AU - Shaw, D. E.

AU - Sigmund, R.

AU - Singer, F.

AU - Skipp, P. J.

AU - Sousa, A. R.

AU - Sterk, P. J.

AU - Sun, K.

AU - van Aalderen, W. M.

AU - Thornton, B.

AU - van Geest, M.

AU - Vestbo, J.

AU - Vissing, N. H.

AU - Wagener, A. H.

AU - Wagers, S. S.

AU - Weiszhart, Z.

AU - Wheelock, C. E.

AU - Wilson, S. J.

PY - 2026/1

Y1 - 2026/1

N2 - 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.

AB - 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.

KW - Asthma

KW - allergic sensitization

KW - asthma diagnosis

KW - cluster

KW - component-resolved diagnostics

KW - network analysis

KW - statistical network analysis

UR - https://www.scopus.com/pages/publications/105012535889

U2 - 10.1016/j.jaci.2025.05.032

DO - 10.1016/j.jaci.2025.05.032

M3 - Article

C2 - 40602688

SN - 0091-6749

VL - 157

SP - 262

EP - 272

JO - Journal of allergy and clinical immunology

JF - Journal of allergy and clinical immunology

IS - 1

ER -

Exploring geographic differences in IgE response through network and manifold analyses

Abstract

Keywords

UN SDGs

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