Mohamed H Shamji1, Irene Thomsen2, Janice A Layhadi3, Jasper Kappen4, Gabriële Holtappels5, Umit Sahiner6, Amy Switzer3, Stephen R Durham3, Oliver Pabst7, Claus Bachert5. 1. Allergy & Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, and the Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden. Electronic address: m.shamji@imperial.ac.uk. 2. Institute of Immunology, Hannover Medical School, Hannover, Germany. 3. Allergy & Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, and the Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. 4. Allergy & Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, and the Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Department of Pulmonology, STZ centre of excellence for Asthma & COPD, Sint Franciscus Vlietland group, Rotterdam, The Netherlands. 5. Upper Airways Research Laboratory, Ghent University, Ghent, Belgium; Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden. 6. Pediatric Allergy Department, Hacettepe University School of Medicine, Ankara, Turkey. 7. Institute of Immunology, Hannover Medical School, Hannover, Germany; Institute of Molecular Medicine, RWTH Aachen, Aachen, Germany.
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.
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.
Authors: Ya Na Zhang; Jia Song; Guan Ting Zhai; Hai Wang; Ren Zhong Luo; Jing Xian Li; Bo Liao; Jin Ma; Heng Wang; Xiang Lu; Da Bo Liu; Zheng Liu Journal: Allergy Asthma Immunol Res Date: 2020-03 Impact factor: 5.764
Authors: Alexandra Starry; Fraence Hardtstock; Thomas Wilke; Julia Weihing; Bernhard Ultsch; Martin Wernitz; Marius Renninger; Ulf Maywald; Oliver Pfaar Journal: Allergy Date: 2022-04-08 Impact factor: 14.710