Understanding IgE-mediated autoimmunity and autoallergy

Sherezade Moñino-Romero¹, Inge Kortekaas Krohn², Yi-Kui Xiang³, Sabine Altrichter⁴, Katrine Baumann⁵, Hafsa Belasri², Monique Butze⁶, Shauni de Vriese², Stefan Frischbutter¹, Jan Gutermuth², Emek Kocatürk⁷, Paolo Maria Matricardi⁸, Melba Muñoz¹, Laurent L Reber⁹, Jörg Scheffel¹, Per Stahl Skov¹⁰, Carolin Steinert¹¹, Nicolas Charles¹², Pavel Kolkhir¹³

Affiliations

¹ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany.
² Vrije Universiteit Brussel (VUB), Skin Immunology & Immune Tolerance (SKIN) Research Group, Laarbeeklaan 103, 1090, Brussels, Belgium; Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Department of Dermatology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium.
³ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
⁴ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Dermatology and Venerology, Kepler University Hospital Linz, Linz, Austria; Center for Medical Research, Johannes Kepler University Linz, Linz, Austria.
⁵ RefLab ApS, Hvidovre, Denmark; Department of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
⁶ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
⁷ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Dermatology, Bahcesehir University School of Medicine, Istanbul, Turkey.
⁸ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁹ Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1291, Centre National de la Recherche Scientifique (CNRS) UMR5051, University of Toulouse, Toulouse, France.
¹⁰ RefLab ApS, Hvidovre, Denmark; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis (ORCA), Odense University Hospital, Odense, Denmark.
¹¹ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Biology, Chemistry and Pharmac, Freie Universität Berlin, Berlin, Germany.
¹² Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Inidex Infibrex, Faculté de Médecine site Bichat, Université Paris Cité, Paris, France.
¹³ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany. Electronic address: pavel.kolkhir@charite.de.

PMID: 41207642
DOI: 10.1016/j.jaci.2025.10.025

Free article

Review

Understanding IgE-mediated autoimmunity and autoallergy

Sherezade Moñino-Romero et al. J Allergy Clin Immunol. 2025.

Free article

. 2025 Nov 7:S0091-6749(25)01115-7.

doi: 10.1016/j.jaci.2025.10.025. Online ahead of print.

Authors

Affiliations

¹ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany.
² Vrije Universiteit Brussel (VUB), Skin Immunology & Immune Tolerance (SKIN) Research Group, Laarbeeklaan 103, 1090, Brussels, Belgium; Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Department of Dermatology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium.
³ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
⁴ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Dermatology and Venerology, Kepler University Hospital Linz, Linz, Austria; Center for Medical Research, Johannes Kepler University Linz, Linz, Austria.
⁵ RefLab ApS, Hvidovre, Denmark; Department of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
⁶ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
⁷ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Dermatology, Bahcesehir University School of Medicine, Istanbul, Turkey.
⁸ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁹ Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1291, Centre National de la Recherche Scientifique (CNRS) UMR5051, University of Toulouse, Toulouse, France.
¹⁰ RefLab ApS, Hvidovre, Denmark; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis (ORCA), Odense University Hospital, Odense, Denmark.
¹¹ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; Department of Biology, Chemistry and Pharmac, Freie Universität Berlin, Berlin, Germany.
¹² Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Inidex Infibrex, Faculté de Médecine site Bichat, Université Paris Cité, Paris, France.
¹³ Institute of Allergology, Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany. Electronic address: pavel.kolkhir@charite.de.

PMID: 41207642
DOI: 10.1016/j.jaci.2025.10.025

Abstract

Chronic inflammatory diseases affect millions of people and are associated with considerable clinical, human, and economic burden. Available treatments have limitations; some are toxic, or they may prevent disease symptoms without affecting pathogenic drivers and disease course. Recent progress in the understanding of chronic inflammation can facilitate the development of targeted and disease-modifying therapy. In particular, IgE autoantibodies against self-antigens are thought to be linked to the pathophysiology and course of chronic inflammatory diseases including atopic dermatitis, asthma, bullous pemphigoid, chronic spontaneous urticaria, and systemic lupus erythematosus. The European Network for IgE-Mediated Autoimmunity (ENIGMA) aims to unravel the role and relevance of IgE autoantibodies in chronic inflammatory diseases. In this review, the ENIGMA consortium presents the concept of IgE-dependent autoimmunity and autoallergy, summarizes current knowledge and its gaps, and focuses on ways to enhance our understanding of these complex processes.

Keywords: Atopic dermatitis; IgE; asthma; autoantibodies; autoimmune diseases; autoimmunity; bullous pemphigoid; chronic inflammatory skin diseases; chronic spontaneous urticaria; systemic lupus erythematosus.

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Conflict of interest statement

Disclosure statement Research funding was received from Fonds Wetenschappelijk Onderzoek (grant G056322N to I.K.K.; and grants G056322N and 18E2K24N to J.G.). Disclosure of potential conflict of interest: I. Kortekaas Krohn reports research funding from AbbVie, Pfizer, and Sanofi/Regeneron. S. Altrichter reports, outside the present report, speaker and/or advisor for and/or research funding from AstraZeneca, Allakos, Biocryst, Blueprint, Celltrion, CSLBehring, Incyte, Kalvista, LeoPharma, Lilly, LeoPharma, Moxie, Novartis, Phavaris, Takeda, Thermo Fisher Scientific, and Sanofi. K. Baumann is an employee of RefLab ApS. J. Gutermuth reports research funding from Sanofi concerning autoreactive IgE; and advisor or speaker for AbbVie, Almirall, Ariez International, Eli-Lilly, Leo-Pharma, and Pfizer. E. Kocatürk reports speaker and advisor for Novartis, Menarini, LaRoche Posey, Sanofi, Bayer, Abdi İbrahim, and Pfizer. P. M. Matricardi reports, outside the present report, research support and speaker’s fees from Thermo Fisher Scientific, Euroimmun, Hycor, and MADX; research funds from Thermo Fisher Scientific, Euroimmun, and Hycor; and consulting fees from Hycor and MADX. M. Muñoz reports, outside the present report, speaker and/or advisor for and/or has received research funding from Jasper, Celldex, Biocryst, Blueprint, Celltrion, Annexon, and Roche. L. L. Reber reports, outside the present report, consulting fees and/or research funding from NEOVACS, Novartis, CEVA, Merus, and Argenx. J. Scheffel reports, outside the present report, conduct of studies for, receipt of research funds and/or advisor for Allakos, Ascilion, AstraZeneca, CSL Behring, Celldex, Genentech, Escient, Novartis, Sanofi, Servier, Septerna, ThirdHarmonicBio, ThirdRock, and Thermo Fisher Scientific. P. S. Skov is founder and scientific advisor of RefLab ApS. N. Charles reports, outside the present report, consulting fees and/or research funding from Argenx and Onward Therapeutics. P. Kolkhirreports, outside the present report, speaker/consultant for BioCryst, Merus, Novartis, Roche, and ValenzaBio. The rest of the authors declare that they have no relevant conflicts of interest.

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Understanding IgE-mediated autoimmunity and autoallergy

Affiliations

Understanding IgE-mediated autoimmunity and autoallergy

Authors

Affiliations

Abstract

Conflict of interest statement

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