Robert Lisak, M.D.
A study by a team of Wayne State University School of Medicine researchers was named one of the 10 best papers on multiple sclerosis research published in 2012 in an article in the Multiple Sclerosis Journal.
“The 'best' basic science paper on multiple sclerosis in 2012,” written by Dr. Don Mahad of the Centre for Neuroregeneration, University of Edinburgh, and published in the July 2013 issue of the Multiple Sclerosis Journal, recognized a study headed by Robert Lisak, M.D., professor of neurology, among the best articles on MS. The WSU study, “Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro,” was published in the May 2012 issue of the Journal of Neuroimmunology.
“The detection of immunoglobulin-independent secretory products of B cells that were cytotoxic to oligodendrocytes by Lisak and colleagues raised interesting avenues for further exploration of the contribution of B cells to the GM pathology of MS,” Dr. Mahad wrote. “Having proposed a potential role for B cells in GM pathology, the next challenge in translating the findings to patients that attend MS clinics is to develop relatively non-invasive techniques to identify MS patients with B cell aggregates.”
“We think that our approach to investigating a novel and unexpected mechanism of how B lymphocytes might contribute to the development of damage to the cerebral cortex in different stages of multiple sclerosis is important and could lead to more focused forms of treatment,” Dr. Lisak said. “We are gratified to see that others are in agreement on the potential importance of this work.”
B cells, a subset of lymphocytes (a type of circulating white blood cell), mature to become plasma cells and produce immunoglobulins, the proteins that are antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping to maintain normal immune function when healthy.
In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges – the covering of the brain and spinal cord – that attract them. Once within the meninges or central nervous system, Dr. Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins, but that damage oligodendrocytes, the cells that produce a protective substance called myelin.
The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and partially why they are attracted to the meninges and the nervous system.
The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, removed the cells from the culture, then collected the material produced. After adding the material produced by the B cells to the brain cells of rats, including the cells that produce myelin, the scientists found significantly more oligodendrocytes died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.
The team is now working to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.
In addition to Dr. Lisak, the research team includes Joyce Benjamins, Ph.D., professor of neurology; Samia Ragheb, Ph.D., assistant professor of neurology and of immunology and microbiology (now assistant professor of Biomedical Sciences at Oakland University William Beaumont School of Medicine); Liljana Nedelkoskaa, research assistant in neurology; and Jennifer Barger, research assistant in neurology; as well as researchers at the Montreal Neurological Institute and McGill University in Montreal.