My research focuses on modelling IgG4-mediated autoimmune diseases. Human immunoglobulin 4 (IgG4), the least abundant IgG in serum, is known for its anti-inflammatory properties. IgG4 exhibits low affinity for most activating Fc receptors on immune cells, weak binding to C1q, and undergoes Fab-Arm Exchange (FAE), resulting in functionally monovalent and bispecific antibodies. Although historically considered benign, IgG4 autoantibodies are the dominant isotype in IgG4-autoimmune diseases (IgG4-AID), affecting various organs. One such disease is MuSK-Myasthenia Gravis (MuSK-MG), characterized by muscle weakness and fatigability, particularly in the neck, facial, and bulbar muscles. Developing treatments for these diseases is challenging due to the lack of a proper IgG4 homolog in rodents, limiting preclinical research. Mouse IgG1 is a potential functional homologue, interacting with Fc receptors and C1q similarly to human IgG4, but lacks the capacity to undergo FAE. Therefore, my project aims to develop a mouse model expressing a human IgG4-like antibody through genetic modification of murine IgG1. This model will be employed to induce pathogenic IgG4 responses through active immunization with IgG4-AID autoantigens, thereby modelling IgG4-mediated autoimmune diseases, including MuSK-MG.

My supervisors are Dr. Maartje Huijbers, Prof. Dr. Silvère van der Maarel and Dr. Peter Hohenstein.

My project is connected to www.huijberslab.org.