Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease

• DOI: 10.3389/fimmu.2022.732977
• Publication Date: 2022-03-15T11:49:17Z
• Authors: Amelie Bos; Esil Aleyd; Lydia P. E. van d...; P. J. Winter; Niels Heemskerk; Stephan M. Pouw; Louis Boon; Rene J. P. Musters; Jantine E. Bakema; Cassian Sitaru; Michel Cogné; Marjolein van Egmond
• Keywords: Immunoglobulin A

Immunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota increasingly appreciated. IgA autoantibodies have been found several autoimmune or chronic inflammatory diseases, but their role pathophysiology ill-understood. can interact with Fc receptor FcαRI on immune cells. We now established novel blistering model, which closely resembles human disease linear bullous (LABD) by using genetically modified mice that produce express FcαRI. Intravital microscopy demonstrated presence anti-collagen XVII, - auto-antigen LABD-, resulted neutrophil activation extravasation from blood vessels into skin tissue. Continued exposure to XVII led massive accumulation, severe tissue damage blister formation. Importantly, treatment anti-FcαRI monoclonal antibodies not only prevented disease, was also able resolve existing inflammation damage. Collectively, our data reveal autoantibody-mediated identify promising new therapeutic target