Autoimmune brain diseases in children cause sudden and severe episodes of inflammation in the brain, spinal cord, and optic nerves. A common autoimmune brain disease in children is called myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). MOGAD often leads to vision loss, weakness, and long-term neurological problems that can impact a child’s life. Although MOGAD is becoming more widely recognized, there are still no FDA-approved treatments for this condition. Families are often left with uncertainty about why the disease happens, how to predict and prevent relapses, and which treatments are most effective. This project seeks to understand how harmful antibodies contribute to inflammation in MOGAD. The research focuses on microglia, the immune cells that live in the brain and normally help maintain a healthy environment. In autoimmune diseases, microglia may become overactive and worsen injury. The research will investigate how anti-MOG antibodies change microglial behavior and why these interactions may lead to more severe disease. By understanding this interaction, the study aims to uncover new targets for treatments that could stop the damaging inflammation. The project also supports the training of a pediatric rheumatologist who specializes in autoimmune brain diseases. Through mentorship and advanced scientific training, the applicant will learn advanced techniques, including antibody sequencing, human antibody production, and spatial transcriptomics. These advanced skills will enable the development of a system for analyzing autoantibodies in pediatric diseases. By combining mouse models of disease and antibodies obtained directly from children with MOGAD, this research will build a clearer understanding of how the disease develops and how to stop it. The long-term goal is to create more effective treatments that improve the lives of children and families affected by autoimmune brain diseases.