Exploring disease heterogeneity in multiple sclerosis: can autoimmune reactivity against a single protein explain much of this diversity?

Multiple sclerosis (MS) is a common chronic neurological disease that is characterized by a diverse range of symptoms and an unpredictable disease course. It is thought that MS is generally caused by autoimmunity directed against various components of central nervous system myelin, a substance that coats the nerve axons and facilitates rapid nerve conduction. The diversity of MS arises from  differences in the location and amount of inflammation and demyelination, the effectiveness of myelin repair mechanisms, and the degree of underlying neuronal and axonal loss. A huge variety of potential mechanisms have been proposed to explain these 3 components. However, taking a more reductionist view, our work suggests that autoimmune reactivity directed against the most abundant myelin protein, proteolipid protein (PLP), can affect all of these components in a fairly large proportion of patients. In this talk, I will discuss those findings, and how we are trying to go about proving definitively that PLP is a major autoantigen in MS.

A/Prof Judith Greer has had a long-standing interest in diseases that affect the nervous system, and, after doing a PhD in cancer immunology at the University of Queensland, she went to work in the Dept of Neurology at Harvard University, where her interests shifted toward neuroimmunology, particularly in relation to multiple sclerosis (MS). After returning to Australia, she set up a neuroimmunology lab in the School of Medicine at UQ. Her research is directly particularly towards trying to identify nervous system components that are targeted by the immune system in people with MS, in determining how immune responses within the nervous system relate to the symptoms experienced by people with MS, and in developing new ways to specifically turn off the damaging immune responses in MS. She also has ongoing interests in immune activation in the nervous system following stroke, and in identifying potential neuronal targets of autoantibodies in people with psychosis. Judith is also interested in research training, and is the Director of Research Training for the Faculty of Medicine at UQ.