多発性硬化症の病因と病態

抄録

Multiple sclerosis (MS) is an immune–mediated inflammatory disease of the central nervous system (CNS), destroying the myelin and the axons to varying degrees. The cause of MS is still unknown, but epidemiological data indicate that both genetic and environmental factors are important for the etiology of MS. It is well known that some major histocompatibility complex haplotypes increase the risk of MS, and environmental factors include Epstein–Barr virus infection, low serum vitamin D level, and smoking. It has been long hypothesized that myelin–reactive T cells access the CNS where they induce an inflammatory cascade that results in demyelination, but this so far remain elusive. Although Th1 cells were previously thought to drive inflammation, Th17 cells are also critically involved in the initiation of disease pathogenesis. Pathological cascade of inflammation correlates with clinical exacerbation ; however, patients gradually develop progressive disease with time, which is characterized by cortical demyelination and neurodegeneration, including neuronal and axonal degeneration. Neuropathological and imaging studies indicate the early and sustained neurodegeneration in MS, indicating both inflammation and neurodegeneration contribute to MS mechanism. However, it is still largely unknown how they interplay over the disease course.