Multiple Sclerosis (Experimental Autoimmune Encephalomyelitis)
Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, including the brain and spinal cord. The disease affects about 350,000 Americans and about 1.1 mil-lion worldwide. Age of onset is typically twenty to forty years old, women are affected more frequently than men (2:1 ratio), and it is most prevalent in indi-viduals of northern European ancestry. It is thought to be mediated primarily by a T-cell-mediated attack on the myelin sheaths of certain nerve fibers, resulting in inflammation, demyelination, and glio-sis (scarring). In addition, autoantibod-ies against components of myelin such as myelin oligodendrocyte glycoprotein (MOG) may be seen and also may con-tribute to disease pathogenesis by fixing complement. During the course of disease, the lesions classically occur at different times and in different locations. Symp-toms include sensory loss, paresthesias (numbness, tingling), visual changes due to optic neuritis, tremor, ataxia, weakness, spasticity, and other neurological symp-toms. Patients with MS can exhibit either a relapsing-remitting or a progressive course.
EAE is a model of MS induced in susceptible animals by immunization by intact myelin or components of myelin, the sheath that surrounds certain neurons. Like CIA for RA, EAE can be induced in several species, including mice, rats, guinea pigs, rabbits, and primates. Although induced by heterologous antigen(s), the disease is autoimmune. Several proteins have been used to induce EAE, including MBP, pro-teolipid protein (PLP), and MOG. Different antigens cause somewhat different clini-cal manifestations. By administering the antigen with complete Freund’s adjuvant and pertussis toxin, the blood-brain bar-rier is disrupted, permitting access by immune cells. The resulting demyelinating disease closely resembles human MS and is thought to be mediated primarily by T cells because disease can be transferred to normal animals by T cells (type IV autoim-mune reaction). There is only limited evi-dence that an immune response to MBP, PLP, or MOG is involved in human disease, and it is hypothesized that other myelin antigens may be the targets of autoreactive T cells in MS.