The Wistar Institute’s Paul M. Lieberman, Ph.D., and lab team led by senior staff scientist and first author, Samantha Soldan, Ph.D., have shown that B cells infected with the Epstein-Barr virus (EBV) can contribute to a harmful, inflammatory state that leads to multiple sclerosis (MS). They have also found a way to specifically target these problematic B cells, which can help reduce the damaging autoimmune response associated with MS.conclusive evidence that Epstein-Barr virus (EBV) contributes to the development of multiple sclerosis (MS). The group has also demonstrated how these problematic B cells can be specifically targeted to reduce the harmful autoimmune response associated with MS. The lab’s research was published in Nature Microbiology in a paper titled “Multiple sclerosis patient derived spontaneous B cells have distinct EBV and host gene expression profiles in active disease.”
EBV, which is typically dormant, affects the majority of the human population, with over 90% of individuals carrying the virus as a silent, usually asymptomatic infection. However, EBV infection has been shown to be convincingly linked to numerous autoimmune diseases, including MS.Linked to numerous illnesses, such as MS: a chronic autoimmune disease that damages the myelin sheath of neurons in the brain and nervous system. The myelin sheath helps with quick nervous system signaling, so its deterioration can lead to a range of symptoms including motor control problems, sensory issues, and speech difficulties.
While scientists understand that EBV can play a role in the onset of MS, the specific ways in which this occurs are still not fully understood.The Lieberman lab is trying to understand the role of EBV in MS development. They worked with Steven Jacobson, Ph.D., of the Neuroimmunology Branch at the National Institute of Neurological Disorders and Stroke, who provided cell line samples from patients. The team studied cell samples from a healthy control group, a group of patients with active MS, and a group of patients with stable MS. They found that B cells, Important cells of the immune system play a key role in regulating the body’s immune responses. They have also been linked to autoimmune diseases because of their ability to signal the immune system to respond. When B cells are infected with EBV, they become immortalized, meaning they are no longer limited by cell aging and can divide indefinitely. This leads to the formation of “lymphoblastoid cell lines,” or LCLs. This immortalized state of B cells can happen naturally in the body as a result of EBV infection, allowing researchers to extract immortalized SLCL samples from the body for study.The researchers obtained matched samples from different groups of patients. Dr. Lieberman and his team then conducted genetic analyses of the SLCLs and found that the MS-positive sample groups had higher expression of genes linked to active EBV, along with increased inflammatory signaling and higher levels of the FOXP1 protein, which was found to promote active EBV gene expression. Their findings suggested that active EBV in MS could be promoting inflammation and disease. Additionally, the group tested several antiviral compounds.study of TAF on SLCL groups revealed that TAF was able to decrease lytic EBV gene expression without causing cell death. Additionally, TAF led to a significant reduction in the expression of inflammatory cytokines such as IL-6 in the SLCLs from patients with active MS. Furthermore, when SLCLs from patients with active MS, stable MS, and controls were treated with TAF along with antiviral T cells, it was observed that the T cell response, which is a key factor in the autoimmune dysfunction of MS, was lowered in SLCLs from MS patients but not in the control group. This suggests that TAF treatment has the potential to be a targeted cytotoxic anti-lytic therapy for MS.”
“Our research involving theSLCLs research indicates that it is possible to target the problematic inflammation signaling caused by lytic EBV in a way that can reduce harmful immune responses,” said Dr. Lieberman. “We are enthusiastic about expanding on this idea; we have the potential to explore whether TAF or other EBV inhibitors could be an effective treatment for multiple sclerosis that can halt autoimmune damage without causing widespread and dangerous cell death.”
