Mechanisms of lesion localization in multiple sclerosis

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Multiple sclerosis (MS) is a chronic disease that affects all areas of the brain and spinal cord (central nervous system or CNS), leading to a huge variety of clinical symptoms and signs, depending upon which parts of the CNS are affected. MS affects about 2 million people worldwide, with the onset of disease often between 20-40 years of age, at a time when family and work commitments are often at their peak. There is no cure for MS, and most people who develop this disease become more and more disabled over their lifetime. MS is an autoimmune disease, i.e. one's own immune system starts to see the CNS as something foreign that needs to be targetted and eliminated. Previously, it has been considered that there are no particular reasons why people with MS develop lesions in the specific parts of the CNS that they do, i.e. it has been thought to be a fairly random event. However, we have recently shown that there are clear correlations between the development of lesions in some parts of the CNS, the particular molecules within the CNS that are being targetted by the immune system, and some genes that control the immune system that are carried by people with MS. The aim of the current study is to work out the mechanism(s) by which autoimmune reactivity targets lesions to different parts of the CNS. We will focus on one target molecule known as myelin proteolipid protein or PLP. People with MS who carry certain immune-related genes are more likely to have immune cells that target PLP, and our work strongly suggests that this subsequently leads to the development of lesions in the brainstem or cerebellum. This work has implications for disease pathogenesis, prognostication and therapy for MS, as a knowledge of patterns of autoimmune reactivity that lead to particular clinical outcomes will improve our ability to give people with MS an idea of they symptoms they might experience and allow specific therapies to be given to patients who will benefit most from them.