Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses - 06/06/19
, Irene Thomsen, PhD d, ∗, Janice A. Layhadi, PhD a, Jasper Kappen, MD, PhD a, f, Gabriële Holtappels b, c, Umit Sahiner, MD g, Amy Switzer, MSc a, Stephen R. Durham, MD, FRCP a, Oliver Pabst, PhD d, e, ∗, Claus Bachert, MD b, c, ∗Abstract |
Background |
Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by local production of polyclonal IgE idiotypes. Although tissue IgE concentrations can be in the range of several thousand kilounits per liter, the regulatory mechanisms by which IgE-mediated inflammation is controlled in patients with nasal polyps are not well understood.
Objective |
We sought to determine whether locally induced IgG antibodies in patients with nasal polyps can inhibit an IgE-mediated proallergic response.
Methods |
Nasal polyp homogenates were collected from patients with grass pollen allergy with CRSwNP and nonallergic control subjects. IgE levels were measured using the Immuno Solid-phase Allergen Chip assay. IgE-containing nasal polyp homogenates with or without IgG depletion were evaluated for their capacity to promote IgE-facilitated allergen presentation, basophil activation, and histamine release. Local IgE and IgG repertoires were evaluated using Immunoglobulin 454 sequencing.
Results |
We show that IgG plays a key role in controlling IgE-mediated inflammatory responses in patients with nasal polyps. Depletion of IgG from nasal homogenates resulted in an increase in CD23-mediated IgE-facilitated allergen binding to B cells but also enhanced FcεRI-mediated allergen-driven basophil activation and histamine release. A similar response was observed in relation to specific IgE antibodies to Staphylococcus aureus enterotoxins. The capacity of IgG in nasal polyps to limit IgE-mediated inflammation is based on the fact that IgG repertoires widely share the antigen targets with the IgE repertoires in both allergic and nonallergic subjects.
Conclusion |
Polyclonal IgE idiotypes in patients with CRSwNP are functional, promote IgE-mediated proallergic inflammation, and are partially antagonized by corresponding IgG idiotypes. This is most likely due to the fact that IgE and IgG clonotypes are widely shared in patients with nasal polyps.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : IgG, antibody repertoire, IgE, chronic rhinosinusitis, nasal polyps, allergic rhinitis
Abbreviations used : CRSwNP, CRTH2, DAO, GPA, IMGT, NAC, SEB, SE, SE-IgE, sIgE, VH
Plan
| Supported by the Imperial College research funds. |
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| Disclosure of potential conflict of interest: M. H. Shamji serves as a consultant for Imperial College London and receives lecture fees from ALK-Abelló, ASIT Biotech, Allergopharma, and UCB. S. R. Durham receives grant support from the Immune Tolerance Network, the National Institute of Allergy and Infectious Diseases, ALK-Abelló, Hørsholm Regeneron, and Biotech Tools and serves as a consultant from Anergis, Circassia, Biomay, Merck, Allergy Therapeutics, Med Update GmbH, and Food Standards. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 143 - N° 6
P. 2086 - juin 2019 Retour au numéro
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