Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease
Immunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota is increasingly appreciated. IgA autoantibodies have been found in several autoimmune or chronic inflammatory diseases, but their role in pathophy...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.732977/full |
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| author | Amelie Bos Esil Aleyd Lydia P. E. van der Steen P. J. Winter Niels Heemskerk Stephan M. Pouw Louis Boon Rene J. P. Musters Jantine E. Bakema Cassian Sitaru Michel Cogné Marjolein van Egmond Marjolein van Egmond |
| author_facet | Amelie Bos Esil Aleyd Lydia P. E. van der Steen P. J. Winter Niels Heemskerk Stephan M. Pouw Louis Boon Rene J. P. Musters Jantine E. Bakema Cassian Sitaru Michel Cogné Marjolein van Egmond Marjolein van Egmond |
| author_sort | Amelie Bos |
| collection | DOAJ |
| description | Immunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota is increasingly appreciated. IgA autoantibodies have been found in several autoimmune or chronic inflammatory diseases, but their role in pathophysiology is ill-understood. IgA can interact with the Fc receptor FcαRI on immune cells. We now established a novel IgA autoimmune blistering model, which closely resembles the human disease linear IgA bullous disease (LABD) by using genetically modified mice that produce human IgA and express human FcαRI. Intravital microscopy demonstrated that presence of IgA anti-collagen XVII, - the auto-antigen in LABD-, resulted in neutrophil activation and extravasation from blood vessels into skin tissue. Continued exposure to anti-collagen XVII IgA led to massive neutrophil accumulation, severe tissue damage and blister formation. Importantly, treatment with anti-FcαRI monoclonal antibodies not only prevented disease, but was also able to resolve existing inflammation and tissue damage. Collectively, our data reveal a novel role of neutrophil FcαRI in IgA autoantibody-mediated disease and identify FcαRI as promising new therapeutic target to resolve chronic inflammation and tissue damage. |
| first_indexed | 2024-12-21T00:06:38Z |
| format | Article |
| id | doaj.art-4af949826139448faa844c9e290be8b0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T00:06:38Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4af949826139448faa844c9e290be8b02022-12-21T19:22:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.732977732977Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated DiseaseAmelie Bos0Esil Aleyd1Lydia P. E. van der Steen2P. J. Winter3Niels Heemskerk4Stephan M. Pouw5Louis Boon6Rene J. P. Musters7Jantine E. Bakema8Cassian Sitaru9Michel Cogné10Marjolein van Egmond11Marjolein van Egmond12Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Research Institute of Amsterdam Institute for Infection and Immunity, Research Institute of Amsterdam Institute for Infection and Immunity, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Research Institute of Amsterdam Institute for Infection and Immunity, Research Institute of Amsterdam Institute for Infection and Immunity, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Research Institute of Amsterdam Institute for Infection and Immunity, Research Institute of Amsterdam Institute for Infection and Immunity, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Research Institute of Amsterdam Institute for Infection and Immunity, Research Institute of Amsterdam Institute for Infection and Immunity, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Research Institute of Amsterdam Institute for Infection and Immunity, Research Institute of Amsterdam Institute for Infection and Immunity, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Research Institute of Amsterdam Institute for Infection and Immunity, Research Institute of Amsterdam Institute for Infection and Immunity, Amsterdam, NetherlandsReseach and Development, JJP Biologics, Warsaw, PolandDepartment of Physiology, Amsterdam UMC, Vrije Universiteit, Amsterdam, NetherlandsDepartment of Otolaryngology/Head-Neck Surgery, Amsterdam UMC, Vrije Universiteit, Amsterdam, NetherlandsDepartment of Dermatology, University of Freiburg, Freiburg, GermanyDepartment of Immunology, University of Limoges, Limoges, FranceDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Research Institute of Amsterdam Institute for Infection and Immunity, Research Institute of Amsterdam Institute for Infection and Immunity, Amsterdam, NetherlandsDepartment of Surgery, Amsterdam UMC, Vrije Universiteit, Amsterdam, NetherlandsImmunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota is increasingly appreciated. IgA autoantibodies have been found in several autoimmune or chronic inflammatory diseases, but their role in pathophysiology is ill-understood. IgA can interact with the Fc receptor FcαRI on immune cells. We now established a novel IgA autoimmune blistering model, which closely resembles the human disease linear IgA bullous disease (LABD) by using genetically modified mice that produce human IgA and express human FcαRI. Intravital microscopy demonstrated that presence of IgA anti-collagen XVII, - the auto-antigen in LABD-, resulted in neutrophil activation and extravasation from blood vessels into skin tissue. Continued exposure to anti-collagen XVII IgA led to massive neutrophil accumulation, severe tissue damage and blister formation. Importantly, treatment with anti-FcαRI monoclonal antibodies not only prevented disease, but was also able to resolve existing inflammation and tissue damage. Collectively, our data reveal a novel role of neutrophil FcαRI in IgA autoantibody-mediated disease and identify FcαRI as promising new therapeutic target to resolve chronic inflammation and tissue damage.https://www.frontiersin.org/articles/10.3389/fimmu.2022.732977/fullFcαRICD89IgAneutrophilsLABD |
| spellingShingle | Amelie Bos Esil Aleyd Lydia P. E. van der Steen P. J. Winter Niels Heemskerk Stephan M. Pouw Louis Boon Rene J. P. Musters Jantine E. Bakema Cassian Sitaru Michel Cogné Marjolein van Egmond Marjolein van Egmond Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease Frontiers in Immunology FcαRI CD89 IgA neutrophils LABD |
| title | Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease |
| title_full | Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease |
| title_fullStr | Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease |
| title_full_unstemmed | Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease |
| title_short | Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease |
| title_sort | anti fcαri monoclonal antibodies resolve iga autoantibody mediated disease |
| topic | FcαRI CD89 IgA neutrophils LABD |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.732977/full |
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