Researchers have identified a disease-associated antibody, aquaporin 4 (AQP-4), in individuals with neuromyelitis optica and neuromyelitis optica spectrum disorders, but few studies to date have examined disease course in seropositive patients. Kitley et al. retrospectively examined 106 AQP-4 seropositive individuals—59 from the United Kingdom and 47 from Japan. Age of onset was an important predictor of disability type, as was ethnicity—not only between U.K. and Japanese groups, but among ethnic subgroups within the U.K. cohort.
Researchers who study multiple sclerosis have long debated whether MS is a bona fide autoimmune disease in part because a clear, disease-causing autoantigen has never been identified despite extensive efforts to find one. In this study, Elliott et al. used a novel assay for the search: They exposed myelinated rat neurons cultured from spinal tissue to blood serum taken from individuals with MS (n = 37), healthy controls (n = 13), and those with other neurological diseases (n = 10) to test whether antibodies in the serum could attack myelin antigens and cause demyelination. They identified pathogenic immunoglobulin G responses in the serum of approximately a third of the MS group but not in serum from any other subjects. This observation suggests that autoantibodies can contribute to demyelination by targeting oligodendrocytes and the myelin sheaths they extend. Three people from that subgroup who had undergone plasma exchange therapy showed significantly reduced demyelinating IgG activity after the procedure. Further work is necessary to determine the relation between the antibodies, such treatment, and disease course.
Neuronal activity demands large amounts of energy and previous work suggests that astrocytes can provide substrates that help power neurons. This paper extends that concept to another type of glial cell, oligodendrocytes, which make the myelin sheaths around axons. Nave’s group genetically knocked out a key portion of the mitochondrial electron transport chain in oligodendrocytes, thus destroying the cells’ usual way of extracting energy. In this situation, the oligodendrocytes utilized a different metabolic pathway for deriving energy, albeit inefficiently; its end product, lactate (which still contains high-energy electrons), passed to the underlying nerve cell. The work suggests a mechanism by which oligodendrocytes support nerve-cell survival and might help explain why nerve cells deteriorate when the myelin sheath is attacked in MS.