A PIONEERING figure in neuroimmunology, Angela Vincent, University of Oxford, UK, was honoured with the Controversies in Neurology (CONy) Excellence in Neurology Award. Known for her groundbreaking research on auto-antibodies and their implications in neurodevelopmental disorders, Vincent has significantly influenced the landscape of neuroimmunology.
Vincent discussed the past, present, and future of antibody-mediated diseases, with an initial focus on myasthenia gravis (MG), an autoimmune disorder in which patient auto-antibodies bind to acetylcholine receptors (AChR) at the neuromuscular junction. Binding of immunoglobulin G (IgG) antibodies leads to the internalisation and destruction of AChR by complement-dependent lysis. Vincent explained that, although severe phenotypes are rare, they can be lethal, such as arthrogryposis multiplex congenita, caused by lack of fetal movement in utero. Vincent highlighted that children who survive arthrogryposis have long-term myopathy, underscoring the importance of early MG diagnosis in mothers. Although 50% of mothers do not have evidence of MG, most have strong antibody reactivity to fetal AChR, and administration of immunotherapies before pregnancy is critical to reduce mother-to-fetus transfer of pathogenic antibodies. She particularly underscored the potential of anti-neonatal Fc receptor monoclonal antibodies, which successfully reduced IgG levels, and are now licensed for use in MG.
Vincent also discussed anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, another autoimmune neurological disease, in which IgG antibodies are directed against NMDAR, initially causing seizures, cognitive defects, and psychiatric manifestations, with symptoms later progressing to autonomic instability and loss of consciousness. She pointed out that immunotherapies can lead to substantial, and even total, recovery of patients with NMDAR encephalitis.
To conclude the session, Vincent shed light on the issue of misdiagnosis in rare diseases, emphasising the necessity of adequate testing and guidelines to avoid false positive results. Furthermore, she noted that not much is known about IgG4 antibodies, as opposed to IgG1 and IgG3, and that the geographic distribution of IgG4-mediated MG could indicate possible environmental influences.
