Causes

Reactivation of ancient viruses incorporated into the human genome in the course of evolution may be involved in the acute inflammatory response that is characteristic of multiple sclerosis (MS), a study says. The findings of the study, “Expression of endogenous retroviruses reflects increased usage of atypical enhancers in…

Vesicles in the blood that contain a protein called fibrinogen important for blood clotting were found to be “sufficient and required” for the occurrence of spontaneous disease relapses in mouse models of multiple sclerosis (MS), a study reports. In mice, these vesicles were associated with immune cell infiltration, inflammation,…

Oligodendrocyte precursor cells (OPCs), the cells responsible for myelin production, are unable to migrate into sites of myelin loss in the brain. These cells then cluster and disrupt the blood-brain barrier (BBB), triggering an inflammatory process in the early stages of multiple sclerosis (MS), a study shows. The study, “Aberrant oligodendroglial–vascular interactions disrupt the blood–brain barrier, triggering CNS inflammation,” was published in the journal Nature Neuroscience. MS is an autoimmune disease characterized by the loss of myelin (demyelination) — the fat-rich substance that protects nerve fibers — which leads to neurodegeneration. Along with loss of myelin, researchers have observed that the blood-brain barrier — a highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation — breaks down in the initial stages of disease. A team led by researchers at the University of California, San Francisco, have now discovered that OPCs are involved in the disruption of the blood-brain barrier in MS, according to a press release from the National MS Society, which funded the study. Oligodendrocytes are myelin-producing cells and are responsible for myelinating the nerve cells’ axons — a single oligodendrocyte is capable of myelinating multiple axons. Mature myelin-producing oligodendrocytes develop from more immature, stem cell-like OPCs. In a normal brain, upon myelin loss, OPCs are called into action and travel into the damage site where they mature and generate myelin-producing oligodendrocytes. In this study, the researchers found that OPCs in MS form clusters in blood vessels of the brain-blood barrier, having lost the ability to detach from these vessels and migrate to injury sites. In an animal model of MS, they saw that OPC aggregates altered the location of other cells — called astrocytes — in a competition for space, and contributed to the disruption of blood vessels. Astrocytes are a group of star-shaped cells, belonging to the group of glial cells, that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation. The team also observed that OPC aggregates trigger an immune inflammatory response, shown by a large number of microglia (the central nervous system immune cells) and immune cells called macrophages around these cell clusters. “We find in several MS cases, in lesion areas with active inflammation, that OPCs can be found clustered on vasculature, representing a defect in single cell perivascular migration and inability to detach from blood vessels,” the researchers wrote. Further molecular analysis revealed that OPCs have high levels of Wnt signaling, and elevated secretion of Wif1 factor to the extracellular space that could explain why OPCs accumulate and destroy the blood-brain barrier. The WiF1 factor is actually a negative regulator of Wnt signaling that is essential for the maintenance of the blood-brain barrier structure. This factor competes with Wnt ligands, and affects the integrity of cellular junctions, making the blood-brain barrier more fragile and permeable. "Evidence for this defective oligodendroglial–vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB,” the researchers wrote. They suggested that more studies are needed to better understand the interactions between blood vessels and oligodendrocytes, which could help identify new therapeutic targets for promoting myelin repair in MS.

Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about MS? Visit our forum. This week’s question is inspired by the forum topic “Tremors Caused by MS” from April 30, 2018. What’s shaking? If you…

The RhoE protein has been identified as being important for axons’  myelination and extension in the central nervous system, two processes that go awry in diseases like multiple sclerosis (MS). The findings stem from Pilar Madrigal’s doctoral thesis, “Role of the small GTPase RhoE in myelination and axonal tracts development.”…

Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about multiple sclerosis? Visit our forum. This week’s question is inspired by the forum topic “Can there be a connection between Epstein-Barr virus…

The herbicide linuron, commonly used with other herbicides, insecticides and fungicides to control the growth of grass and weeds, may be an important environmental risk factor in the development of neurological diseases that include multiple sclerosis, researchers suggest. Used in the U.S. and other countries — but recently…

Children exposed to certain air pollutants in urban areas or some household chemicals are at higher risk of developing multiple sclerosis (MS) during childhood or adolescence, two new research studies suggest. The studies “Urban air quality and associations with pediatric multiple sclerosis” and…

Environmental changes, such as high temperatures and alterations in salt types and concentrations, trigger structural changes to myelin that may increase the risk of multiple sclerosis (MS), according to a new study. The research, “Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions,” was…

An enzyme produced by bacteria in the gut was seen to activate immune cells linked to the development and progression of multiple sclerosis, a finding that may pave the way for a vaccine that might alter autoimmune mechanisms involved in MS. The study, “…

Lymphatic vessels, the “roads” that work to clear waste material from the brain, can also carry messages that direct immune system attacks against myelin, promoting the onset of multiple sclerosis (MS), new study shows. While the identity of these messages remains unknown, the findings suggest that blocking these signals could…

When the following headline in the Australian newspaper the Herald Sun caught my eye recently, I was cautiously intrigued: “Doctors believe they have discovered the cause of multiple sclerosis” My cynical heart didn’t go pitter-patter as…

Lately, much of my work has been focused on the relationship between the gut and MS. As I experience ongoing gut issues, I need to learn how to advocate for myself by learning as much as I can about gut bacteria and finding the right…

Long-term exposure to three common air pollutants — fine particulate matter, nitrogen dioxide, and ozone — were not found to be “convincingly” linked to incidence of multiple sclerosis (MS) in a large population study conducted in Canada. The study, “Long-term exposure to air pollution and the incidence of multiple sclerosis: A…

Analysis of post-mortem brain samples from multiple sclerosis (MS) patients and healthy individuals (without neurologic disease) showed that while signs of Epstein-Barr virus (EBV) infection are present in both groups of brains, EBV-positive immune cells were more prevalent and densely populated in the MS brain. The study reporting those findings,…

Infection with lymphocytic choriomeningitis virus triggers expression of a factor called TOX in immune cells strengthening their migration into the brain and promoting damaging effects, including inflammation and tissue destruction. These findings represent a new piece of the puzzle about the mechanism underlying autoimmune diseases  like multiple sclerosis (MS).

Exposure to fracking chemicals during pregnancy may aggravate multiple sclerosis (MS) severity and induce an earlier start of symptoms, a new study in mice suggests. The study, “Developmental Exposure to a Mixture of 23 Chemicals Associated With Unconventional Oil and Gas Operations Alters the Immune System…

Exposure to epsilon toxin (ETX), which is mainly found in livestock, could be linked to the development of multiple sclerosis (MS), new research suggests. The study, “Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis,” appeared in the Multiple Sclerosis Journal. ETX is one of…

Infection with the common Epstein-Barr virus (EBV) may increase the risk of developing multiple sclerosis (MS), a new report from the  Cincinnati Children’s Hospital Medical Center says. Besides MS, the Epstein-Barr virus also raises the risk for six other disorders: systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory…

People who live in areas with medium to high levels of ultraviolet-B (UV-B) radiation from sunlight during their childhood and early adolescence, or in the years preceding the age of onset of multiple sclerosis (MS), have a lower risk of developing the disease, according to researchers. The study’s findings…

United Arab Emirates scientists have found active Epstein-Barr virus in many multiple sclerosis patients’ brain cells, supporting the notion that it plays a role in the disease. The team found it in two types of brain cells — astrocytes and microglia. The virus can be active or lie dormant in…

A global collaboration of researchers led by Belgium’s Flanders Institute for Biotechnology has determined the structure of the pro-inflammatory cytokine IL-23 and its receptor IL-23R, which could be potential targets for treating multiple sclerosis (MS) and other autoimmune diseases. Their study, “Structural Activation of Pro-inflammatory Human Cytokine…

Iranian researchers have identified another herpes virus that may increase the risk of a person developing multiple sclerosis. The team identified the human herpesvirus 6, or HHV6, as a potential risk factor for MS through a meta-analysis of several studies. They published their findings, “Relationship of Human…

A large U.K. survey assessing the frequency of chickenpox and shingles in multiple sclerosis (MS) patients suggests a link between these diseases and MS, researchers report, suggesting their findings could help in decisions regarding immunosuppressive treatments and varicella-zoster virus vaccinations. Results of the study “Prevalence of a history of…

Exposure to certain gut bacteria at a young age may cause multiple sclerosis (MS) and fuel its progression, a new mouse study shows. The study, “Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood,” appeared in the journal Proceedings of the National…

Having a concussion when you’re 11 to 20 years old could increase your risk of developing multiple sclerosis later, a Swedish study suggests. The collaboration between Örebro University and Karolinska Institutet showed that a concussion in adolescence raised the risk of developing MS by 22 percent. Two or more concussions…

Past infection with the Epstein-Barr virus (EBV) has been reported to increase the risk for multiple sclerosis (MS). Now, researchers have found a link between EBV and MS in three racial-ethnic groups, with African-Americans and Latinos showing a higher risk for MS than Caucasians.

A new and potentially important mechanism in the development of autoimmune diseases like multiple sclerosis was discovered by scientists at the University of Freiburg, Germany. They identify a protein, called Caveolin-1, that is essential to immune cells called B-cells working as intended to protect a person from pathogens or — in its absence…

Secondary progressive multiple sclerosis (SPMS) patients have larger quantities of certain antibodies to the stomach ulcer bacterium Helicobacter pylori than those with relapsing-remitting multiple sclerosis (RMSS), finds a Greek study which also showed that MS patients in general differ from healthy people in this aspect. Although researchers at the University of Thessaly think…

A gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases like multiple sclerosis, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) report. It's a discovery that, they said, appears to be "a big step in the right direction." According to the study, published in the journal Science Immunology, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. “We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” Ciriaco Piccirillo, the study's lead author and an immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release. Tregs are known to be the immune system players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions. The FOXP3 gene is also well-known, and documented, to be essential for proper Treg cell function. However, the mechanisms by which FOXP3 gene is involved in Treg cell activities are still poorly understood. In the study, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions,” the research team — in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan — evaluated the impact of a FOXP3 gene mutation in autoimmunity response. Taking advantage of cutting-edge technology, the team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. “What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” said Piccirillo. “Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” added Khalid Bin Dhuban, the study's first author and a postdoctoral fellow in Piccirillo’s laboratory. The team developed a compound capable of restoring Treg cells' ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, two chronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including multiple sclerosis, type 1 diabetes, and lupus. "Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," said Piccirillo. “Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.” “This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Piccirillo added. “With this discovery, we are taking a big step in the right direction.”