Their attacks were singular events or diagnosed as monophasic NMO. In one study ( Kitley et al., 2014), the team found that patients who tested positive for MOG on a short-length cell-based assay generally had a good prognosis. Jacqueline Palace, M.D., of Oxford University and her team are developing several permutations of the assay sensitive to different lengths of MOG. Then they expose antibody-cell complex to secondary antibodies with fluorescent tags to visualize the complex. Researchers use human or other mammalian cells to express the MOG antigen on the cell membrane, then expose the cells to diluted serum or cerebrospinal fluid. Douglas Sato, M.D., Ph.D., of Tohoku University in Japan illustrated the basic process of the assay in an email to MSDF. Labs in Japan, Austria, Switzerland, and the United Kingdom are refining and standardizing a cell-based assay for identifying MOG antibodies in NMOSD patients. This research got the ball rolling on more specific cell-based assays for MOG and helped illuminate its potential role in anti-AQP4-seronegative NMOSD patients. “Antibodies recognize conformational epitopes,” he said, “so the protein has to be folded.”īut in 2007, Kevin O’Connor, Ph.D., of Yale University and his team developed a tetramer radioimmunoassay with greater sensitivity to the MOG antibody, an assay that’s highly attuned to MOG’s conformation. In an interview with MSDF, Weinshenker explained that ELISA and western blot assays unfold and stretch out proteins along a gel, making it harder for the antibodies to recognize the protein. Traditionally, researchers and clinicians use western blot and ELISA assays to find the MOG antibody, but these assays lead to conflicting results. One of the major challenges in studying MOG in humans is that assays for the antibody often lead to nonspecific results and false positives. As myelin breaks down, it may expose MOG to the immune system in a novel way, triggering the release of antibodies. Some think its presence could be a sign of the disease rather than a feature of its pathogenesis. But anti-MOG has a much spottier record in multiple sclerosis, and the jury is still out on whether and how it is involved in demyelination ( O’Connor et al., 2007 Mayer and Meinl, 2012). The same antibody did not produce similar results in healthy animals. Furthermore, early research demonstrated that a monoclonal antibody (8–18C5) attacked MOG, leading to dramatic demyelination in experimental autoimmune encephalomyelitis mice. The glycoprotein sits atop the outermost layer of myelin, making it an easy target for autoimmune attack. MOG has captivated and confounded multiple sclerosis researchers for quite some time. So far, researchers believe these patients are clinically distinct from the anti-AQP4 patients and may even represent a new disease. Many of them presented their data at the joint ACTRIMS-ECTRIMS meeting in Boston earlier this month. A small group of labs from Asia and Europe recently confirmed an antibody for myelin oligodendrocyte glycoprotein (MOG) in the sera of some of these anti-AQP4 negative patients. On the other hand, the small subset of NMOSD patients who are seronegative for anti-AQP4 tend to fare better. The body seems to attack the optic nerves and spinal cord, leading to problems in vision and walking. Relapses and disabilities are common, while recovery from the attacks tends to be incomplete. Unfortunately, anti-AQP4-positive patients usually receive a dire prognosis. According to Brian Weinshenker, M.D., of the Mayo Clinic in Minnesota, roughly 70% to 80% of adult NMOSD patients test positive for AQP4. AQP4 is an integral membrane protein that helps conduct water through the cell membrane. While researchers understand NMOSD far better than they did even 10 years ago, so much remains obscured.Īs we described in our four-part News Synthesis on NMO, researchers and clinicians believed NMO to be a subtype of multiple sclerosis until 2005, when researchers discovered a biomarker for the disease in an antibody that attacks a protein in astrocytes known as aquaporin-4. NMOSD is an umbrella category including optic neuritis, myelitis, and acute disseminated encephalomyelitis (ADEM). Scientists understand neuromyelitis optica spectrum disorders (NMOSD) far better now than when they were first described as Devic’s disease in 1894.
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