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Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation

Cellular & Molecular Immunology volume 17, pages 426–429 (2020)Cite this article

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Basophils are rare granulocytes. Despite representing only ~0.5% of all leukocytes, basophils have several important physiological functions.1,2 Although basophils lack the classic features of professional antigen-presenting cells,3,4,5,6,7 through the secretion of cytokines, they orient the immune response by polarizing Th2 differentiation and supporting B-cell differentiation and class switching. Basophils are also critical for mediating protection against helminth infection.1,2,8,9

Basophils receive activation signals from diverse sources. It is well recognized that cytokines such as IL-3, granulocyte–macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP) and IL-33; various toll-like receptor ligands; allergen-bound IgE provide activation signals to basophils and induce the release of inflammatory mediators.10,11,12,13,14,15 In addition, several reports have also demonstrated the existence of anti-IgE autoantibodies that possess the capacity to induce basophil activation in patients with chronic spontaneous urticaria (CSU), atopic or non-atopic asthma or autoimmune disease.16,17,18,19,20,21 However, isolation and functional exploration of such anti-IgE IgG autoantibodies from either healthy donors or patients have not been attempted yet. By using a pooled normal IgG preparation from healthy donors, specifically intravenous immunoglobulin G (IVIG)22 that represents the complete IgG repertoire of a normal individual, we attempted to address this outstanding question in the field.

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Fig. 1: Anti-IgE IgG autoantibodies isolated from IVIG induce basophil activation.

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Acknowledgements

This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université, Université Paris Descartes, ANR-19-CE17-0021(BASIN), and CSL Behring, Switzerland. C.G. and A.K. were the recipients of fellowships from La Fondation pour la Recherche Médicale (FDM20150633674 and FDT201805005552, respectively), France. We thank the staff of the Centre d’Histologie, d’Imagerie et de Cytométrie, and Centre de Recherche des Cordeliers for their help, and F. Carrère at Royan Hospital for providing the IgE myeloma serum.

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Author notes

  1. These authors contributed equally: Caroline Galeotti, Anupama Karnam

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, F-75006, France

    Caroline Galeotti, Anupama Karnam, Jordan D. Dimitrov, Srini V. Kaveri & Jagadeesh Bayry

  2. Service de Rhumatologie Pédiatrique, Centre de Référence des Maladies Auto-Inflammatoires Rares et des Amyloses, CHU de Bicêtre, le Kremlin Bicêtre, F-94270, France

    Caroline Galeotti

  3. Université Paris Descartes, Sorbonne Paris Cité, Paris, F-75006, France

    Jordan D. Dimitrov, Srini V. Kaveri & Jagadeesh Bayry

  4. Laboratoire d’Immunologie et d’Allergologie; CHU d’Angers, Université d’Angers; INSERM Unité 1232; LabEx IGO “Immuno-Graft-Onco”, Angers, F-49933, France

    Alain Chevailler

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  1. Caroline Galeotti
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Contributions

J.B. designed the study. C.G. and A.K. performed the experiments. C.G., A.K., J.D., S.V.K., and J.B. analyzed the data. A.C. provided essential tools. J.B. drafted the paper, and all the authors edited and approved the final version of the paper.

Corresponding author

Correspondence to Jagadeesh Bayry.

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Competing interests

This work is supported in part by a research grant from CSL Behring, Switzerland.

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Galeotti, C., Karnam, A., Dimitrov, J.D. et al. Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation. Cell Mol Immunol 17, 426–429 (2020). https://doi.org/10.1038/s41423-019-0334-x

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