Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease.

Autor:	Bos A; Department 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, Netherlands., Aleyd E; Department 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, Netherlands., van der Steen LPE; Department 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, Netherlands., Winter PJ; Department 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, Netherlands., Heemskerk N; Department 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, Netherlands., Pouw SM; Department 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, Netherlands., Boon L; Reseach and Development, JJP Biologics, Warsaw, Poland., Musters RJP; Department of Physiology, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands., Bakema JE; Department of Otolaryngology/Head-Neck Surgery, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands., Sitaru C; Department of Dermatology, University of Freiburg, Freiburg, Germany., Cogné M; Department of Immunology, University of Limoges, Limoges, France., van Egmond M; Department 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, Netherlands.; Department of Surgery, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Mar 15; Vol. 13, pp. 732977. Date of Electronic Publication: 2022 Mar 15 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.732977
Abstrakt:	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. Competing Interests: Author LB was employed by company JJP Biologics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Bos, Aleyd, van der Steen, Winter, Heemskerk, Pouw, Boon, Musters, Bakema, Sitaru, Cogné and van Egmond.)
Databáze:	MEDLINE
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